Background: Traffic-related pollution is associated with the onset of asthma and the development of different phenotypes of asthma. Few studies have investigated the association between traffic proximity and late-onset of asthma (LOA) and early-onset asthma (EOA). This study was conducted to investigate the associations of LOA phenotypes with a function of the distance between residence and heavy traffic roads (HTRs).Methods: The study group consisted of 280 patients who were (LOA: 78.4%) recruited consecutively from a pay-for-performance asthma program to clarify the patient characteristics and proximity to HTRs within 1,000 m from their residences between EOA and LOA in three urban centers in Taiwan. The subsequent analysis focused on patients with LOA (n = 210) linking phenotypes and distance to HTRs.Results: Subjects with LOA tended to be older than those with EOA and had shorter asthma duration, poorer lung function, lower atopy, and less exposure to fumes or dust at home. Patients with LOA were more likely than those with EOA to live within 900 m of two or more HTRs . Among patients with LOA, minimum distance to an HTR was negatively associated with numbers of specific IgE as well as positively associated with the age of onset and body weight significantly. A higher proportion of patients with atopy  and anxiety/depression  and a trend of lower proportion of patients with obese  were found to be living within 900 m from HTRs.Conclusions: Late-onset of asthma (LOA) tended to live in areas of higher HTR density compared to EOAs. Among patients with LOA living close to HTRs, the interaction between traffic-related pollution, allergy sensitization, and mood status were the factors associated with asthma onset early. Obesity may be the factor for later onset who live far from HTRs. After an initial appearance in childhood, asthma may remain inactive for an extended period or reappear later in life. A number of recent studies have also described the onset of asthma during adulthood . Thus, eDespite the non-negligible incidence of adult-onset asthma, the causes have not been extensively investigated. Identifying the risk factors of LOA is crucial to understanding the underlying mechanisms and LOA was identified as the most significant independent risk factor for non-remission in patients with asthma . It shouIn the current study, we were interested in whether the traffic proximity was different in EOA and LOA. We sought to determine whether proximity or density of HTRs is associated with the LOA in the asthma cohort of an urban medical center. We also examined patient characteristics in order to identify factors significantly associated with traffic proximity in LOA.https://www.nhi.gov.tw/Content_List.aspx?=nEBDEAEDEC639490C&topn=5FE8C9FEAE863B46). Inclusion criteria included the diagnosis of asthma by a pulmonologist in accordance with ICD-10 code J45 at least twice within 90 days. Note that diagnoses were based on episodic respiratory symptoms , variable or persistent obstructive pulmonary function, and response to asthma therapy. All patients provided written informed consent. The study protocol was approved by the Chang Gung Medical Foundation Institutional Review Board (No. 201900211B0).This was a cross-sectional study of asthma patients recruited consecutively in a pay-for-performance program at Chang Gung Memorial Hospital, Linkou branch, which has been implemented by the National Health Insurance Administration (NHIA) in Taiwan since 2001 . CertifiAt the initial recruitment, we recorded the characteristics of the subjects based on questionnaires or medical records, including age at the time of asthma diagnosis by a physician, asthma control test (ACT) results, family history of asthma, the use of asthma medication, co-morbidities, childhood history of dyspnea, frequency of bronchitis, exposure to fumes or dust at home or work, smoking status, and current residence (in the last 6 months). Pulmonary function and allergy-related biomarkers, including eosinophils, eosinophil cation protein (ECP), immunoglobulin E (IgE), and specific IgE  were recorded. Patients with any positive specific IgE to allergens  were considered atopic. The tests above were done at physicians' discretion in real-world practice. For example, according to the regulation of Taiwan healthcare insurance, the reimbursement of specific IgE would not be offered unless the total IgE > 25 KU/L. Therefore, a test of specific IgE was not mandatory and the numbers of sIgE to check were based on the physicians' discretion.n = 58) and LOA (n = 210). This group of urban patients was subjected to further analysis to determine the proximity to HTRs within 1,000 m from their residences . Based on the geographic distribution of patients, we selected the ten busiest traffic monitoring sites, each of which had a daily mean bidirectional PCU exceeding 36,329 in 2018 (Heavy traffic roads (HTRs) were identified using open-data daily PCU (Passenger Car Unit) statistics from the Directorate General of Highways of Taiwan ( in 2018 .https://www.openstreetmap.org/export). Data covered the region between latitudes from 24.74 to 25.33 N and longitudes from 120.86 to 122.04 E. All map data other than roads and streets were excluded. Criteria for the selection of routing vectors were based on the Top-10 PCU routes. We sought to mitigate sphere projection bias by re-projecting the coronadite system of geometrics  from EPSG:4326  to EPSG:32651 (WGS 84 – UTM Zone 51N). This converted the spherical representation in radian units into a 2D flat surface presentation in meters, which is a convenient format for subsequent calculation. Geodata was processed using a custom script written in JavaScript under the NodeJS  runtime environment, and all exchangeable data formats were standardized according to GeoJSON format. The graphical representation of input variables and calculation results was handled using QGIS software .Geometric data were extracted from maps obtained from the open-data service – Open Street Map  was used to calculate the minimum distance between the domicile of each patient and the nearest HTR based on geometric data . We alsoSD or percentage. The Student's t-test was used to compare the means of continuous variables and normally distributed data; otherwise, the Mann-Whitney test was used. Categorical variables including patients with EOA and LOA living in ≥ 1 or 2 heavy-traffic roads within indicated distance were tested using the Chi-square test or Fisher exact test. For tests done by physicians' discretion, the numbers are tested were smaller than the total cohort. The analysis was done on the patients who were checked and the number of participants who provided information and the number of participants with positive results were specified. Unadjusted odds ratio (OR) and 95% CI were calculated for selective variables in geometric analysis during the Chi-square test. The association between the minimum distance to an HTR and patient factors was tested using the Spearman rank correlation because the distance was not normally distributed. All analysis was performed using IBM SPSS Statistics version 19. Armonk, NY: IBM Corp. Statistically significant results were defined as p ≤ 0.05.All data were expressed as mean ± 1) were lower in patients with LOA than in patients with EOA. As for allergic biomarkers, IgE levels were significantly higher in the EOA group than in the LOA group. The proportion of patients with ECP levels exceeding the normal range (18 μg/L) was higher in the EOA group than in the LOA group. The two groups were comparable in terms of eosinophil count. Patients with EOA tended to be more atopic and were also more susceptible to home dust mite (HDM), cat dander, and dog dander than patients with LOA  were LOA. with LOA .p = 0.07). We further analyzed the number of HTRs within regions that were measured from patient residences at set distances of up to 1,000 m. When patients resided with a distance of 900 m in the high-traffic road, more patients with LOA were living in multiple HTRs areas compared to patients with EOA , more positive atopic status , and a higher sensitivity to HDM .As shown in p = 0.025), BMI (p = 0.023) as well as negatively correlated with the numbers of positive specific IgEs (p = 0.005).To clarify the influence of high traffic density on patients with LOA, we conducted further analysis on the correlation between the distance to HTRs and patient characteristics in the LOA group . The minp = 0.001, unadjusted OR: 2.82, 95%CI: 1.519–5.235. p = 0.047, unadjusted OR: 1.81, 95%CI: 1.031–3.165. p = 0.075, unadjusted OR: 1.974, 95%CI: 0.936–4.165. For the binary variables and confirming the results of the correlation test, we compared the atopy, mood status, and obesity (BMI ≥ 30) of patients with LOA living within or beyond 900 m of HTRs . A higheOur analysis revealed that patients with LOA tended to be older than patients with EOA, to have had asthma for a shorter duration, were less likely to have a family history of asthma, were less exposed to fumes or dust in the home, were less likely to be atopic, were less sensitive to common inhaled allergens, and were more likely to have poor lung function. In urban areas, more patients with LOA had multiple HTRs (≥ 2 HTRs) within a distance of 900 m. Patients living within 900 m from multiple HTRs had a higher total IgE level, a more atopic status, and a higher sensitivity to HDM, compared to patients with ≥ 1 HTRs at a comparable distance. Among patients with LOA, the minimum distance to an HTR was positively associated with the age of onset and BMI and was negatively associated with atopy and mood status. Among patients with LOA, a higher proportion of atopic patients were living within 900 m from HTRs, a higher proportion of patients with anxiety or depression were living within 900 m from HTRs and a trend of a higher proportion of obese patients were living beyond 900 m from HTRs. To the best of our knowledge, this is the first study demonstrating the different traffic density between EOA and LOA and different phenotypes in LOA by geolocation, which showed the novel relation between asthma phenotypes and the urban environment.Correlation between TRAP and asthma is usually assessed in terms of pollutant concentration, such as nitrogen oxide and particulate matter (PM), or the distance to HTRs. Numerous cohort studies have demonstrated a positive association between exposure to TRAP and the risk of asthma , 29, 30;The patient profiles revealed by the subgroup analysis of patients living with multiple HTRs provided one of the possible mechanisms of asthma inception of LOA . PatientAnxiety and depression contribute to asthma symptoms and stressful life events have been shown as the risk factor of onset of asthma , 38. SomThe incidence of obesity in patients with LOA was higher among those living >900 m from HTRs than among those living <900 m from HTRs . This coThe study has several limitations. First, the cohort had a smaller patient number of EOA compared to LOA. This is because we recruited adult patients consecutively without selection in the pay-for-performance program to prevent selection bias. The higher ratio of LOA to EOA in our cohort is possible due to the remission rate of EOA being much higher than LOA and LOA is suggested to be more severe than EOA , 42. TheIn conclusion, the characteristics of patients with LOA were distinct from those of patients with EOA. By geolocation in urban centers, we discovered the correlation between asthma phenotypes and the urban environment in LOA. patients with LOA tended to live in areas of higher HTR density, which was associated with an elevated incidence of atopic symptoms, sensitivity to HDM, and mood disorder. Proximity to HTRs and obesity may be factors contributing to uncontrolled asthma in cases of LOA. The novel evidence of patient-environment interaction provides further explanation for asthma persistence in the modern world.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Chang Gung Medical Foundation Institutional Review Board (No. 201900211B0). The patients/participants provided their written informed consent to participate in this study.T-YL: conceptualization, data curation, investigation, formal analysis, and writing of the original draft. Y-SL: methodology, software, formal analysis, and visualization. H-CL: data curation, resources, and formal analysis. S-ML: data curation, resources supervision, formal analysis, and writing with review and editing. Y-LL, C-HW, P-JC, and C-YL: data curation and resources. All authors contributed to the article and approved the submitted version.Y-SL is employed by BalDr Strategic Consulting (Hong Kong) Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Objective: Hemifacial spasm (HFS) is a kind of motor disorder, and the striatum plays a significant role in motor function. The purpose of this study was to explore the alterations of the cortical-striatal network in HFS using resting-state functional magnetic resonance imaging (fMRI).Methods: The fMRI data of 30 adult patients with primary unilateral HFS (15 left-side and 15 right-side) and 30 healthy controls were collected. Six subregions of the striatum in each hemisphere were selected for functional connectivity (FC) analysis. One-sample t-test was used to analyze the intragroup FC of the HFS group and the control group. Two-sample t-test was used to compare the difference of FC between the two groups. The correlation between the abnormal FC and severity of HFS was evaluated by using the Spearman correlation analysis.Results: Compared with the controls, the striatal subregions had altered FC with motor and orbitofrontal cortex in patients with HFS. The altered FC between striatal subregions and motor cortex was correlated with the spasm severity in patients with HFS.Conclusion: The FC of the cortical-striatal network was altered in primary HFS, and these alterations were correlated with the severity of HFS. This study indicated that the cortical-striatal network may play different roles in the underlying pathological mechanism of HFS. Hemifacial spasm (HFS) is a syndrome of involuntary contraction of facial muscles innervated by ipsilateral facial nerves , which cAs part of the extrapyramidal system, the striatum is integral to the motor, cognitive, and emotion regulation functions . The subvia the cortical-striatal loop and the dopamine system, and therefore plays a significant role in some motor disorders, including Parkinson’s disease and Huntington’s disease  index has been used in most previous studies to indicate time-domain coherence between neighboring voxels in the brain. Researchers have found ReHo abnormalities in the motor cortex, frontal lobes, and cerebellum in patients with HFS , and no In this study, we performed FC analysis of 12 striatal subregions in patients with HFS. We hypothesized that in patients with chronic primary HFS, the FC between the striatum and motor cortex and FC between striatal subregions will be changed. Since long-term HFS may result in psychological problems, such as depression and anxiety , we alsoA total of 60 subjects were selected from a total of 64 participants, and 4 subjects  were excluded from the analysis due to excessive head motion . Then, 30 patients with HFS  were enrolled from 2017 to 2019 in the Department of Neurosurgery, China-Japan Friendship Hospital. HFS was diagnosed by two experienced neurologists based on clinical symptoms and history. The severity of HFS was assessed using the Cohen spasm scale  . The incThe experiment was carried out on the 3.0 T MRI scanner  with an 8-channel phased-array head coil. The resting-state fMRI with a single-shot gradient recalled echo-planar imaging sequence was performed with the following recipe. The repetition time (TR) was 2,000 ms, while the echo time (TE) was set to 30 ms. The slice thickness was chosen to be 3.5 mm with a spacing of 0.7 mm. The matrix of the image was 64 × 64, while the field of view (FOV) was 224 mm × 224 mm. The flip angle was 90°, and the number of excitations (NEX) was set to 1. A total of 8 min were consumed for each data with 34 slices and 240 time points. T2WI scan was used to exclude the cerebral organic lesions. 3D T1WI anatomic images were reconstructed using three-dimensional fast spoiled gradient-echo sequences (3D FSPGR), and the TR of which was 6.7 ms, while the TE was set to minimum full. The matrix was changed to 256 × 256 with a FOV of 256 mm × 256 mm. Furthermore, the slice thickness was chosen as 1.0 mm, while the NEX remained to be 1.To unify the affected side of the patients, the T1WI and fMRI data with left HFS (15 cases) and matched controls (15 cases) were flipped from left to right before preprocessing . In thisThe regions of interest (ROIs) were determined by the “Define ROI” module using DPARSF software, based on the radius and MNI spatial coordinates. According to the previous study, six striatal subregions of each hemisphere were selected as ROIs, and the radius of each ROI was set to 3 mm. The MNI coordinates of the ROIs were as follows: dorsal caudal putamen , dorsal rostral putamen , ventral rostral putamen , dorsal caudate , inferior ventral striatum , and superior ventral striatum  . The diaz transformation was performed to improve the normal distribution of the data. Then, the correlation map, that is, the FC map of the whole brain was generated for further statistical analysis.First, the time course of the average BOLD signal was extracted from each ROI. Then, the Pearson’s correlation between the time course of each ROI and the time course of all other voxels in the brain was calculated. Fisher t-tests (default mask) were performed in the HFS group and the HC group. The statistical threshold was set at z > 3.6594 and cluster size of >6 mm3, which corresponded to a corrected P < 0.001. This correction threshold was determined using Monte Carlo simulations with the program AlphaSim in AFNI . The Gaussian random field (GRF) method was used for multiple comparison corrections, and the statistical threshold was set at voxel-level P < 0.005 and cluster-level P < 0.05. The DPABI software was used to perform the statistical analysis of FC.To determine the FC differences of the cortical-striatal network between the two groups, two-sample z value of brain regions with significant changes in the HFS group was extracted to explore the relationship between the severity of HFS and altered connectivity. Then, the Spearman correlation analysis was performed using GraphPad Prism 6.0 software to evaluate the correlation between abnormal FC and spasm severity in patients with HFS. The age, sex, education, and duration were regressed as covariates. We also explored the relationship between duration and spasm severity through Spearman correlation analysis, and the age, sex, and education level were regressed as covariates as well. A total of 14 correlations were performed, with 13 abnormal FCs correlating with spasm severity, and, finally, 1 correlation was performed between spasm severity and disease duration. The false discovery rate (FDR) method was used to correct the results of the correlation analysis for multiple comparisons.The z transformation, a 12 × 12 FC matrix was generated for every subject. A total of 66 z values were constructed, and each z value stands for the FC between two brain regions. Two-sample t-tests were performed using SPSS 20.0 software  to compare the difference of FC between the HFS group and the HC group. Age, gender, and education were regressed as covariates. FDR correction was used to control false positives for multiple comparisons, and the statistical threshold was set at P < 0.05.The FC between the striatal ROIs was also calculated. After Fisher P > 0.05)  .The intragroup FC maps of the cortical-striatal network were similar in the HC and HFS groups, which is consistent with previous studies . The putThe contralateral DCP had significantly decreased FC with ipsilateral SFG, SMA, and precentral gyrus, respectively, in the HFS group compared with the HC group .The contralateral DRP had significantly increased FC with contralateral middle frontal gyrus (MFG) and SFG, in the HFS group compared with the HC group .There was no significant alteration in FC between VRP and cerebral cortex in the HFS group compared with the HC group.The contralateral DC had significantly decreased FC with bilateral cerebellar lobule VIII, IX, and contralateral cerebellar crus II, in patients with HFS than that in controls .In the HFS group compared with the HC group, the ipsilateral VSi had significantly increased FC with bilateral OFC, paracentric lobule, and SMA , while tThe ipsilateral VSs showed significantly increased FC with bilateral SMA and paracentric lobule, in the HFS group compared with the HC group . The FC r = −0.433, P = 0.0168 uncorrected)    . Furtherrrected) . There wrrected) . After FP = 0.0053, P = 0.0272 uncorrected), and the FC between contralateral DCP and contralateral VRP was also increased (P = 0.017 uncorrected)  . After FThis study investigated the functional alterations of the cortical-striatal network in patients with HFS and their relationship with clinical manifestations. Compared with the controls, the striatal subregions had altered FC with motor and OFC in patients with HFS. Furthermore, the FC between the ventral striatum and motor cortex was positively associated with the severity of HFS. Finally, our results suggest that the cortical-striatal network may play differential roles in the underlying pathological mechanism of HFS.As we know, this is the first resting-state fMRI study to examine intrinsic cortical-striatal connectivity in HFS. The emotion-related cortex showed significantly increased FC with the ventral striatum and putamen, in patients with HFS compared with the controls. The orbitofrontal lobe and the VSi are involved in emotional activities . The strWe also found that the FC between the putamen and the ipsilateral motor cortex was decreased in the HFS group, and so does the FC between the caudate and the cerebellum. It was known that the precentral gyrus was the first somatic motor area, and the SFG was the premotor area. One side of the cerebral motor area dominates the contralateral body movement, but the muscles involved in associated movement are dominated by bilateral motor areas, such as extraocular muscles and masticatory muscles . The decP < 0.05). However, using a less conservative threshold (P < 0.05), we found that the FC between the putamen ROIs was increased in patients with HFS compared with the controls. Interestingly, a study of the striatal network in facial palsy found the decreased FC between the putamen and the ventral striatum (uncorrected)  , which iThere were several limitations in this study. First, the sample size of this study was small, including patients with left HFS and right HFS. To control the problem on the different sides of the lesion, we flipped the left HFS group from left to right. In the future, the changes of brain functional networks in patients with left and right HFS can be studied separately on the basis of expanding the sample size. Second, this study used a cross-sectional study design to explore the changes of the cortical-striatal network in patients with HFS. Longitudinal studies can be conducted in the future to explore the mechanism of brain network changes in different stages of HFS. Finally, previous studies and our study have all found functional abnormalities in the emotion-related cortex in patients with HFS. Therefore, increasing the evaluation of the psychological status of patients may make the results more reliable, which can be added in further studies.Primary unilateral HFS induces several FC alterations in the cortical-striatal network, specifically, the striatal subregions have altered connectivity with motor and OFC in patients with HFS, respectively. The severity of HFS is associated with these functional alterations. This study provides significant evidence that the altered cortical-striatal connectivity is involved in differential neural mechanisms of motor and emotional dysfunction in patients with HFS.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Ethics Committee of China-Japan Friendship Hospital. The patients/participants provided their written informed consent to participate in this study.GM conceived and designed the experiments. WG and DY performed the experiments. WG and ZZ analyzed the data. WG, LD, BL, JL, YC, YW, XL, AY, KL, and JX discussed the data. WG wrote the manuscript. DY revised the manuscript. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To investigate the difference in character strengths (CSs) between patients with and without polycystic ovary syndrome (PCOS) and the association between biological  and psychological factors .A total of 99 women divided into PCOS (49) and non-PCOS (50) groups who presented to the gynecological clinics at the women’s center in the American University of Beirut Medical Center in 2017 were included. Women were assessed for testosterone bioavailable levels and completed a questionnaire that included Hospital Anxiety and Depression Scale and Values in Action Survey-72. Univariate and multivariable analyses were performed to examine the association of CSs between the two groups and its predictors.The scores of hope, judgement, perspective, and transcendence of the PCOS group were significantly higher in comparison with healthy participants. An increase in free androgen index was negatively correlated to the score of judgement only.Women with PCOS have their own profile of character strengths and virtues that constitute judgement, hope, perspective, and transcendence. This in turn can be utilized to reinforce those personality strengths and thus decrease the psychological distress and mood disorders accompanied with this disease. Polycystic ovarian syndrome (PCOS) is a hyperandrogenic heterogeneous endocrine disorder that affects 15–20% of women in their reproductive age when using Rotterdam criteria . FurtherPCOS is characterized by chronically augmented androgens, specifically free testosterone levels . TestostRecently, the role of character strengths (CSs), within the field of positive psychology, has gained increasing interest and attention in patients dealing with chronic illnesses . As a coThis was a descriptive study performed using a cross-sectional research design of 99 participants in 2017. It was conducted in the gynecological clinics at the women’s center at the American University of Beirut Medical Center (AUBMC). The study was approved by the Institutional Review Board (IRB) of the American University of Beirut (AUB) (SBS-2017-0491). Written informed consent form was obtained from each participant. The study with its objectives and procedures were fully explained and discussed with each subject before administering the questionnaires.The 99 participants were divided into two groups: PCOS (49) and non-PCOS (50). For the PCOS group, participants were eligible for this study if they met the following requirements: women of child-bearing age (18–45 years old) who met 2 out of 3 criteria of the Revised Rotterdam Consensus for PCOS . All controls included women with normal fertility or subfertility due to tubal, male factor or unexplained cause, who did not fit the Rotterdam criteria and were not on contraceptive or anti-androgen pills. Exclusion criteria for the PCOS group included endocrine disorders such as congenital adrenal hyperplasia, Cushing’s syndrome, menopause, androgen secreting tumors, thyroid dysfunction, hyperprolactinemia, type 2 diabetes mellitus, impaired glucose tolerance, concomitant cardiovascular disease, liver and renal dysfunction, and the use of any medication that interferes with endocrine and psychiatric parameters. Besides, patients with any physical disability, clinically proven psychiatric disease, or cut-off score of Hospital Anxiety and Depression Scale (HADS), assessed by a psychiatrist, were excluded.2). To measure biological hyperandrogenism, venous blood sampling for testosterone bioavailable levels [testosterone and sex hormone-binding globulin (SHBG)] were taken. For clinical assessment of hyperandrogenism, hirsutism score was calculated according to Ferriman and Gallwey (1961) scoring system. The participants were evaluated according to body hair on 9 regions from scale 0 (no hair) to 4 (frankly virile), and these were summed to provide an overall hirsutism score. The result was considered either normal , mild , or moderate to severe hirsutism . Moreover, pelvic ultrasound was administered by the primary physician to provide a report of polycystic ovaries.Body mass index (BMI) was calculated as body weight divided by the square of the body height  Survey-72:The sociodemographic data included: age, weight, height, socioeconomic class (income), employment, education, marital status, number of children, smoking status, alcohol consumption, infertility, hirsutism, and personal and family medical history.The HADS was used to assess psychological distress. It is a reliable and valid self-reported questionnaire consisting of 14 questions in a 4-point-likert scale which assesses the overall severity of anxiety and depression (7 questions each). The cut off points are 10 and 7 for depression and anxiety, respectively. Participants who scored high on HADS were informed by their primary physician regarding any significant results.The VIA Survey-72 , a shortData was analyzed using SPSS 25 statistical software package . Descriptive statistics were used to report the sample demographic characteristics. T-test analyses were performed to examine the association of the character strengths and virtues between the two groups. Moreover, multiple linear regression analyses were used to assess the predictors and their contributions to the scores of character strengths and virtues. The significance was set at 0.05.Table 1 depicts this information. . In addition to this, t-test results showed that there was a significant difference (p < 0.05) in the transcendence score between the two groups. However, none was present for the other 5 virtues . Among the 99 female participants, there were 49 women with PCOS and 50 without. The age of non-PCOS women had a mean ± SD of 28.1 ± 5.3 years, while that of PCOS women was 25.0 ± 4.7 years. Regarding their educational level, the majority (63.3%) of PCOS group had a bachelor’s degree (or higher) which was lower than that of non-PCOS group (82.0%). As for employment, only 51.0% of PCOS participants were employed which is much lower in comparison to that of non-PCOS participants (90.0%). Moreover, most of PCOS and non-PCOS groups had a household monthly income between 1,000$ and 2,000$ . The percentage of alcohol intake was lower in PCOS participants (8.0%) than that of non-PCOS (26.0%). In contrast, the smoking history was approximately similar between the two groups. To better understand the personality and psychological profile of PCOS women and its association with biological markers, we compared the character strengths between PCOS and non-PCOS groups. We found that higher scores of hope, judgement, perspective, and transcendence were present within the PCOS women sample.Various previous studies revealed the association of psychopathology in PCOS sample population , 20. HowTestosterone exerts activational and organizational influences on brain structures and its behavior among both sexes . AlthougTo the best of our knowledge, this was the first study to ever assess the character strengths profile and its predictors in a sample group of PCOS women. We found that, of the 24 CSs, PCOS patients had higher scores of judgement, hope, and perspective than the healthy controls. As for the 6 virtues, only transcendence score was shown to be significantly higher in the PCOS group. According to Peterson and Seligman (2004), judgement is considered a corrective strength such that it counteracts faulty thinking . PerspecIn the present study, we performed regression analyses to find out predictors of character strengths’ scores related to the symptoms of their condition. Our findings showed that acne and hirsutism were negatively associated with the appreciation of beauty and excellence score. In fact, Bazarganipour et al. indicated that hirsute PCOS women had poorer body image . FAI wasOur study has some limitations worth noting. Although there was no mean difference between the two studied groups, the sample size was small. Another limitation was the implementation of the project in gynecologic clinics of one hospital. Thus, the PCOS sample might not be an appropriate representation of other PCOS women. Moreover, the present study was the first work to reveal a certain character strengths profile along with its predictors among PCOS women. This calls for population-wide studies to establish normative scores of each of VIA elements, as well as future large, multicenter studies on PCOS women to confirm the findings of our study.In conclusion, we showed that women with PCOS have higher scores of judgement, hope, perspective, and transcendence as character strengths in comparison with healthy patients. We suggest that it is essential for PCOS patients to be referred to psychiatric consultations and undergo positive psychology therapy to enhance their character strengths from the onset of diagnosis. This might be a cost-effective, efficient prophylactic means for adapting with the syndrome and preventing psychopathological disorders associated with PCOS women on the long run. Prospective studies in larger groups are warranted to assess this issue.S1 Table(DOCX)Click here for additional data file.


Lung cancer is the most common cancer and cause of cancer death in Canada, with approximately 50% of cases diagnosed at stage IV. Sociodemographic inequalities in lung cancer diagnosis have been documented, but it is not known if inequalities exist with respect to immigration status. We used multiple linked health-administrative databases to create a cohort of Ontarians 40–105 years of age who were diagnosed with an incident lung cancer between 1 April 2012 and 31 March 2017. We used modified Poisson regression with robust standard errors to examine the risk of diagnosis at late vs. early stage among immigrants compared to long-term residents. The fully adjusted model included age, sex, neighborhood-area income quintile, number of Aggregated Diagnosis Group (ADG) comorbidities, cancer type, number of prior primary care visits, and continuity of care. Approximately 62% of 38,788 people with an incident lung cancer from 2012 to 2017 were diagnosed at a late stage. Immigrants to the province were no more likely to have a late-stage diagnosis than long-term residents : 1.01 : 0.99–1.04), adjusted relative risk (ARR): 1.02 (95% CI: 0.99–1.05)). However, in fully adjusted models, people with more comorbidities were less likely to have a late-stage diagnosis (adjusted relative risk (ARR): 0.82 (95% CI: 0.80–0.84) for those with 10+ vs. 0–5 ADGs). Compared to adenocarcinoma, small cell carcinoma was more likely to be diagnosed at a late stage , and squamous cell  and other lung cancers  were more likely to be diagnosed at an early stage. Men were also slightly more likely to have late-stage diagnosis in the fully adjusted model . Lung cancer in Ontario is a high-fatality cancer that is frequently diagnosed at a late stage. Having fewer comorbidities and being diagnosed with small cell carcinoma was associated with a late-stage diagnosis. The former group may have less health system contact, and the latter group has the lung cancer type most closely associated with smoking. As lung cancer screening programs start to be implemented across Canada, targeted outreach to men and to smokers, increasing awareness about screening, and connecting every Canadian with primary care should be system priorities. Lung cancer is currently the most common cancer and the most common cause of cancer death in Canada, with approximately 30,000 new diagnoses and 20,000 deaths in 2020 . UnfortuCurrent literature on social inequalities in lung cancer stage of diagnosis suggests that certain demographic groups may be appropriate target populations for interventions. Canadians with low incomes have been found to be more likely to be diagnosed with lung cancer at a late stage than those with high income; the same holds true for Canadian men versus women . In the In this population-level retrospective cohort study, we used Ontario health and administrative databases to compare the stage of diagnosis (dichotomized as early vs. late) of lung cancer for immigrants to Ontario versus long-term residents of the province and to examine the association of stage of diagnosis with potentially actionable sociodemographic and health-related factors. We used several databases available at ICES. ICES is an independent, non-profit research institute funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. As a prescribed entity under Ontario’s privacy legislation, ICES is authorized to collect and use health care data for the purposes of health system analysis, evaluation, and decision support. Secure access to these data is governed by policies and procedures that are approved by the Information and Privacy Commissioner of Ontario. ICES houses a secure array of Ontario’s health-related administrative data. Data include population demographics and health service use information on all Ontario residents who are eligible for the province’s universal Ontario Health Insurance Plan (OHIP). All datasets are linked using unique encoded identifiers and analyzed at ICES.The Immigration, Refugee and Citizenship Canada Permanent Resident (IRCC) database consists of detailed demographic information on Ontario’s immigrants and refugees who landed from 1985 onward, including country of birth, date of landing, and immigrant class. The Ontario Cancer Registry (OCR) documents data on all Ontario residents who have been newly diagnosed with or died of cancer (except non-melanoma skin cancers), including the primary cancer site, diagnosis date, age at diagnosis, stage at diagnosis, histology, and cause of death if applicable. To determine the stage at diagnosis, Collaborative Staging is used where available . The ColOther databases that we used included the Registered Persons Database (RPDB), which includes date of birth, sex, postal code, dates of contact with the healthcare system and date of death if applicable; the OHIP Database, which contains procedural and diagnostic codes claimed by physicians in the province; the Client Agency Program Enrolment (CAPE) database which is updated bi-monthly and identifies all Ontarians who are enrolled with a family physician in Ontario’s various primary care models ; the CorWe included all people 18–105 years of age residing in Ontario who were diagnosed with an incident lung cancer as per the OCR at any time between 1 April 2012 and 31 March 2017 and who had a unique ICES identifier. We excluded those whose cancer was stage 0 or in situ at the time of diagnosis, who had no Ontario healthcare system contact for the three years prior to diagnosis, and whose eligibility for provincial health insurance was after their diagnosis date. As more than 90% of Canada’s immigrants live in urban settings [® case-mix system (V10.0) to categorize comorbidity [For each patient, we documented sex, age, and postal code at the time of diagnosis from the RPDB. We used the postal code to identify the income quintile for their neighborhood based on the 2016 Canadian Census mean household income data. We used Aggregated Diagnosis Groups (ADGs) from the Johns Hopkins ACGorbidity . This caorbidity . We also system V.0 to catorbidity .Outcomes were dichotomous: early (I–II) vs. late (III–IV) stage diagnosis based on the OCR.We described the cohort, overall and by immigrant status, on the basis of the variables noted above. We further stratified each of these groups by early vs. late stage of diagnosis and again described them based on the variables noted above. We used chi-square tests and standardized differences (preferable for large sample sizes) for group comparisons and considered a standardized difference of > 0.10 to be clinically important .We used modified Poisson regression with robust standard errors to examine the risk of late vs. early stage of diagnosis among immigrants compared to long-term residents, first unadjusted, then age and sex-adjusted (age as a continuous variable), and then fully adjusted for age, sex, neighborhood-area income quintile, number of ADG comorbidities, cancer type, number of prior primary care visits, and UPC index. We removed cohort members with missing outcome data from the analysis. We also stratified each model by age category, by sex, and by age × sex category. We conducted statistical analyses using SAS software . The study was approved by the Research Ethics Board at Unity Health Toronto.For the overall cohort, 26.5% were diagnosed at an early stage, 62.2% were diagnosed at a late stage, and 11.3% were missing stage. Immigrants and long-term residents did not significantly differ by stage of diagnosis: 25.7%, 63.5%, and 10.8% of immigrants were diagnosed early, late, or had missing stage data, respectively, versus 26.6%, 62.0%, and 11.4% of long-term residents. In bivariate analyses , for botIn regression analyses, immigrants had no differences in stage of diagnosis than long-term residents . People In this population-based retrospective cohort study in urban areas of Ontario, Canada, we found that more than 62% of people with an incident lung cancer from 2012 to 2017 were diagnosed at a late stage. In the context of a universal healthcare system, immigrants to the province were no more likely to have a late-stage diagnosis than long-term residents, and the diagnostic stage was not associated with immigrant class, region of origin, or years in Canada. However, in fully adjusted models, late-stage diagnosis was associated with male sex, fewer comorbidities, and being diagnosed with small cell carcinoma.Our finding that the majority of lung cancers in Ontario are diagnosed late highlights the urgent need for a diagnostic stage shift. Lung cancer is typically diagnosed symptomatically in the Canadian context, and both the lack of specific symptoms and lack of awareness of symptoms can contribute to a delay in diagnosis ,14. OrgaIn fully adjusted models, we found that people with more comorbid conditions had a diagnostic stage advantage. In bivariate analyses, having more primary care contact in the two years prior to diagnosis was also associated with a stage advantage. We have previously found similar findings in Ontario for the stage of diagnosis for colorectal cancer, another prevalent cancer with high mortality , and othSmall cell carcinoma is known for its aggressive nature and early metastasis , and thuThis study has several limitations. First, cancer type was unknown for more than 28% of the study population, and thus, our findings regarding cancer type must be interpreted with caution. Second, immigrants who arrived before 1985 or who first migrated to another province before Ontario are not captured in the IRCC database and are thus included in the long-term resident group. Third, although we looked at the region of origin for immigrants, this obscures unique aspects about country of origin. For example, Newbold et al. found adjusted odds ratios of smoking as low as 0.30 (95% CI 0.26–0.36) for Jamaican-born immigrants and as high as 1.09 (95% CI 0.86–1.40) for Chilean-born immigrants versus Canadian-born . In the As lung cancer screening becomes more commonplace, future research should continue to monitor for inequalities in the stage of diagnosis and inequalities in screening rates. For Ontario’s current organized screening programs , immigrants and people living with low income have lower uptake ,26,27,28Lung cancer in Ontario is frequently diagnosed at a late stage. Immigrant status in Ontario is not associated with a late-stage diagnosis. However, men, people with fewer comorbidities, and people with small cell carcinoma have a higher likelihood of late-stage diagnosis. As lung cancer screening programs start to be implemented in Canada, targeted outreach to men and to smokers, increasing awareness about screening, and connecting every Canadian with primary care need to be system priorities.


Coprococcus was found to be increased in VD while being decreased in MD. Roseburia and Faecalibacterium were increased in MD while being decreased in VD. Importantly, changes in genera Coprococcus, Roseburia and Faecalibacterium should be subjected to intense investigation as markers for physical and mental health.An essential role of the gut microbiota in health and disease is strongly suggested by recent research. The composition of the gut microbiota is modified by multiple internal and external factors, such as diet. A vegan diet is known to show beneficial health effects, yet the role of the gut microbiota is unclear. Within a 4-week, monocentric, randomized, controlled trial with a parallel group design (vegan (VD) vs. meat-rich (MD)) with 53 healthy, omnivore, normal-weight participants , fecal samples were collected at the beginning and at the end of the trial and were analyzed using 16S rRNA gene amplicon sequencing . Alpha diversity as well as beta diversity did not differ significantly between MD and VD. Plotting of baseline and end samples emphasized a highly intra-individual microbial composition. Overall, the gut microbiota was not remarkably altered between VD and MD after the trial.  The gut microbiota is the entirety of all gastrointestinal microorganisms  resident in the human gastrointestinal tract ,2. An esRecent publications dealing with short-term changes in the gut microbiota after becoming vegan are widely lacking. In a small cross-over trial comparing nine healthy subjects on a pre-cooked meal vegan diet (VD) or a pre-cooked meal meat-rich diet (MD), diet was able to modify the gut microbiota rapidly and distinctly . The plaThe monocentric, controlled, randomized trial with a parallel group design with healthy participants was conducted between April and June 2017 at the Center for Complementary Medicine, University Medical of Freiburg, Germany. The study protocol was approved by the ethical committee of the University Medical Center of Freiburg, Germany (EK Freiburg 38/17), and was performed according to the principles of the Declaration of Helsinki. The trial was prospectively registered with the German Clinical Trial register (DRKS00011963). All participants gave written informed consent before inclusion in the study.Study population. Healthy, normal-weight, omnivorous subjects between 18 and 60 years of age, living in Freiburg for more than 6 months, without regular intake of medication, and with no clinically relevant allergies or food intolerance, were enrolled. Exclusion criteria were a history of eating disorders or being on a plant-based diet, participation in another clinical trial, and blood donation in the 4 weeks before the start of the trial, as well as the use of recreational drugs, nicotine, or alcohol. Participants had to be able to speak and understand German and to complete a nutritional protocol. Subjects were recruited via bulletins and newspaper announcements, and potentially eligible subjects were invited for a personal visit to check eligibility criteria in detail.Intervention and control. For standardization, all subjects had to follow a one-week-long run-in phase with a balanced mixed (omnivorous) diet according to the recommendations of the German Nutrition Association (DGE) . AfterwaFecal samples were collected in a special stool collector after the run-in phase but before being assigned to VD or MD (“baseline”) as well as after finishing the trial (“end”). Participants received the collectors after inclusion and were told to fill them immediately before meeting the study staff. Stool samples were frozen and stored at −80°C after receipt. Analysis of stool samples was performed at the Medical University Graz, Austria, according to an established protocol . In brieFasting blood samples were taken after the run-in phase but before being assigned to VD or MD as well as after finishing the trial. Serum from each participant was aliquoted in 1.5-mL, non-diet-labeled cryovials. All methods were previously established and validated. Measurement of concentration of thrombocytes, neutrophilic granulocytes, and monocytes was performed by the Central Laboratory of the University Medical Center of Freiburg. Measurement of branched-chain amino acids was performed by the Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, University Medical Center of Freiburg.Sequences were processed within the QIIME2 framework . The demAll downstream analyses were conducted in R-Studio (R v.3.6.3) . Data weTo assess the alpha diversity of the bacterial communities, commonly used similarity indices were evaluated, considering both richness and evenness, to describe the diversity within samples. For species richness, the Chao1 index, a metric based on the number of observed taxa, was calculated. Taking microbial diversity and richness into account, the Shannon index was calculated, a metric based on the weighted abundance of microbes in each sample. The Inverse Simpson index, considering relative abundance, and Fisher’s index, quantifying the relationship between number and abundance of species, were also calculated. All indices were computed on the unfiltered ASV-level data. To test for differences in alpha diversity between baseline and end samples in each diet, a paired Wilcoxon signed rank test was applied.Principal coordinate analysis (PCoA) was used to visualize differences in community composition among the two diets and their respective baselines. To assess microbial similarity between samples based on the abundance profiles of shared taxa between each pair of samples, Bray–Curtis dissimilarity was applied. Moreover, weighted and unweighted UniFrac distances were calculated to quantify similarity based on (weighted) phylogenetic relationships between each pair of samples .p-Values were corrected for multiple hypothesis testing with the Benjamini–Hochberg method and are referred to as padj.To test for differences in the proportion of samples in which a taxon was detected, logistic regression was applied. The effects of diet, time, and the interaction of diet and time were estimated. The main effects in each diet assessed the change over time within a diet, e.g., “enriched in MD” or “depleted in MD”, while the interaction effects assessed the difference in one intervention compared to the other, e.g., “enriched in MD and depleted (or constant) in VD”. p-Values were corrected for multiple hypothesis testing with the Benjamini–Hochberg method and referred to as padj.To identify differentially abundant bacterial taxa in both diets with respect to their baseline, a zero inflated negative binomial regression model (ZINB) was utilized. This model from the pscl R-package  takes thMetagenomic functions were predicted with the PICRUSt2 algorithm . Based oOut of 150 interested persons, 53 were randomized and started the trial. The study flow is shown in p = 0.001), protein , and fiber  differed significantly between VD and MD. Extensive results of nutritional intake were published previously and showed additional significant differences in vitamin and micronutrient intake  [Descriptive data of all participants are shown in tamin E) . Forty-fpVD = 0.770, pMD = 0.629). The Shannon index, considering richness and evenness within the samples, did not reveal any significant difference in baseline and end, neither for VD nor MD . Moreover, the Inverse Simpson index, based on the relative abundance of species as well as Fisher’s index, quantifying the relationship between number and abundance of species, did not change between baseline and end samples in either diet . Hence, MD and VD had only a minor impact on the heterogeneity of microbial composition, emphasizing the intra-individual stability of participants.Alpha diversity analysis did not differ significantly between VD and MD . For theBray–Curtis dissimilarity revealed no clustering of the samples according to dietary intake and timepoint. For most participants, baseline and end samples appeared to be close together on the PCoA plot, pointing towards a highly individualized and heterogeneous microbial composition a. The siResults of UniFrac distances are shown in Coprococcus between MD and VD. The proportion of samples in which Coprococcus was detected increased in VD from 42% at baseline to 81% at the end of the trial (padj = 0.047), while in MD, it decreased from 69% at baseline to 50% at the end of the trial  and Roseburia faecis, which are depleted in VD, and Blautia (unspecified species) as well as Faecalibacterium (another unspecified species), which are enriched in MD (marked in red in meta data column for sample proportion).As for most ASVs, the signal resulted from less than 10% of all samples; we filtered for the most abundant ASVs observed in at least 40% of samples. These are Bacteroides, Clostridium, Faecalibacterium, and Roseburia were enriched in MD and depleted in VD after the trial   in VD . Therefo < 0.05) , we foun samples a, and instridium b. Interend in MD b.We did not find any MetaCyc pathways, EC numbers, or KEGG orthologs to be significantly enriched in VD or MD at the end of the trial.As discussed in p = 0.130). While, in Phylo1, end samples from VD were overrepresented, in Phylo2, the shift was towards the MD end samples.Analyzing the sample composition within Phylo1 and Phylo2, we found that while baseline samples from VD and MD were almost evenly distributed within each of the two groups, there was a slight, but non-significant, shift in sample composition after the trial . Parabacteroides was present in 63% of all samples in Phylo1 and only in 23% of all samples in Phylo2 (padj < 0.001).To further understand the nature of Phylo1 and Phylo2, we looked at differences in microbial composition by applying logistic regression. We found that the taxa o Phylo1 c. While Bacteroides, Faecalibacterium prausnitzii, and Blautia. Under the assumption that ASVs presented in a large proportion of the samples are the most relevant, we filtered for those significantly differentially abundant ASVs that were also detected in at least 40% of all samples. Here, we found two ASVs of genus Bacteroides and four ASVs of genus Blautia that were more abundant in Phylo2 compared to Phylo1  or BMI (p = 0.454) of participants, but with gender (p = 0.042). In Phylo 2, female samples were overrepresented (71%), while in Phylo 1, gender was equally distributed.The splitting of samples in Phylo 1 and Phylo 2 was not significantly associated with the age (p = 0.842), neutrophilic granulocytes (p = 0.775), and thrombocytes (p = 0.142) were not significantly associated with the splitting into Phylo 1 and Phylo 2.Changes in the concentration of monocytes  were mainly from the family of Lachnospiraceae, which is an interesting observation. Lachnospiraceae are a family of anaerobic, fermentative, and carbohydrate-metabolizing bacteria probably playing a role in metabolic and inflammatory diseases [The difference in the gut microbiota after short-term nutritional change to VD or MD was not fundamental as sample composition did not differ significantly in terms of alpha and beta diversity, but we found a few, mostly highly individual-dependent differences between VD and MD in single ASVs. Most of our participants showed a similar microbiota composition at the start and at the end of the trial, emphasizing the intra-individual stability of the gut microbiota towards diet change. The observed changes in ASVs were attributed to a few participants, predominantly in ASVs occurring in less than 40% of samples. The remaining genera , small effects may not be significant due to limited statistical power. Moreover, clinical trials with fecal samples are always error-prone as the collection of samples depends on the compliance of participants, and the time between bowel movement and further processing is crucial for the results . All of Coprococcus, Roseburia, and Blautia, mainly from the family of Lachnospiraceae, were found to be different between VD and MD after the 4-week trial. These results are interesting as these genera are often discussed to be markers for physical and mental health. The results indicate that VD and MD might have a potentially beneficial effect, including on potentially harmful bacteria, but to a highly individualized extent. The results emphasize the necessity for further research considering a participant’s individual gut microbiota response.The gut microbiota of healthy participants was overall not remarkably changed after transition to VD or MD for four weeks. Analyses of alpha and beta diversity showed high inter-individual gut microbiota variation among participants. Several diet-related ASV changes were observed after the trial, but most of them were only detectable in a few of the samples, emphasizing the highly individual response to nutritional change. Three genera, namely


Backgrounds: Influenza vaccination could decrease the risk of major cardiac events in patients with chronic obstructive pulmonary disease (COPD). However, the effects of the vaccine on decreasing the risk of ventricular arrhythmia (VA) development in such patients remain unclear.Methods: We retrospectively analyzed the data of 18,658 patients with COPD (≥55 years old) from the National Health Insurance Research Database from January 1, 2001, to December 31, 2012. After a 1:1 propensity score matching by the year of diagnosis, we divided the patients into vaccinated and unvaccinated groups. Time-varying Cox proportional hazards regression was applied to assess the time to event hazards of influenza vaccination exposure.Results: The risk of VA occurrence was significantly lower in the vaccinated group during influenza season and all seasons . Among patients with CHA2DS2-VASc scores  of 2–3, receiving one time and two to three times of influenza vaccination were associated with lower risk of VA occurrence in all seasons . Among patients without stroke, peripheral vascular disease, and diabetes, a lower risk of VA occurrence after receiving one and two to three times vaccination was observed in all seasons. Among patients with a history of asthma and patients without a history of heart failure, ischemic heart disease, angina hypertension, or renal failure, a significantly lower risk of VA occurrence was observed after the first time of vaccination in all seasons.Conclusions: Influenza vaccination may be associated with lower risks of VA among patients with COPD aged 55–74. Further investigation is still needed to resolve this clinical question. Chronic obstructive pulmonary disease (COPD) is a worldwide health burden and has risen from the sixth to the third most common cause of death in the past 30 years . StudiesInfluenza is a common and severe viral infection among patients with COPD. It increases the risk of not only acute respiratory failure but also acute cardiovascular events . The risThe National Health Insurance (NHI) program established in 1995 provides health insurance coverage for more than 98% of the Taiwanese population (more than 23 million people). The NHI Research Database (NHIRD) is maintained by the Health and Welfare Data Science Center and has been extensively analyzed and validated by earlier studies . In Taiw2DS2-VASc score; COPD severity (defined as COPD-related inpatient visits)  ; COPD me visits) .2DS2-VASc score), COPD severity and treatment , and medication use .The potential confounders of our cohort were based on sociodemographic characteristics , comorbidities . Regarding female patients with COPD, no significant reduction in VA occurrence was observed between the vaccinated and unvaccinated groups in all seasons, influenza season, and non-influenza season.In the main model, there was no significant difference in VA occurrence after receiving one time, two to three, and more than four times influenza vaccination during the influenza season . In the During non-influenza season, there was no significant difference in VA occurrence after receiving one, two to three, and more than four times of vaccination . Among p2DS2-VASc scores of 2–3, a significantly lower risk of VA occurrence was observed after receiving one time and two to three times of vaccination. In patients with a history of asthma, a significantly lower risk of VA occurrence was observed after the first time of vaccination (aHR: 0.33 [95% CI: 0.14–0.78]). In patients without heart failure, ischemic heart disease, hypertension, angina, and renal failure, significant lower risk of VA occurrence was observed after first time of vaccination .During all seasons, a significant lower risk of VA occurrence was observed after receiving one time of vaccination in the main model (aHR: 0.58 [95% CI: 0.36–0.93]) . There wDuring influenza season, non-influenza season, and all seasons, with more than two times of COPD-related inpatient visits, there was no significant difference of risk of VA occurrence after receiving one, two to three, or more than four times of vaccination. During all seasons, a lower risk of VA occurrence among patients without COPD-related inpatients after the first time of vaccination was observed (aHR: 0.48 [95% CI: 0.25–0.92]). In addition, among patients with one time of COPD-related admission, a lower risk of VA occurrence was associated with more than two times of vaccination (aHR: 0.23 [95% CI: 0.06–0.79]).2DS2-VASc score, and  in Taiwan and Taipei Medical University-Shuang Ho Hospital (Grant No. 109TMU-SHH-21).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To explore the application value of health education combined with aerobic exercise in patients with mastitis found in physical examination.  The clinical data of 100 patients with mastitis who underwent physical examination in the physical examination center of our hospital from October 2020 to October 2021 were retrospectively analyzed. According to the order of physical examination, they were equally split into experimental group and control group. The control group received the routine clinical intervention, while the experimental group received health education combined with aerobic exercise to evaluate the clinical effects of different intervention modes on patients with mastitis. P < 0.001), lower scores of breast pain, skin color, and local mass diameter (P < 0.001), and a higher SF-36 score (P < 0.001).  Compared with the control group, the experimental group after intervention achieved notably higher scores of CD-RISC, self-management ability, and mastitis-related knowledge ( The clinical intervention combining health education with aerobic exercise in patients with mastitis found in the physical examination is an effective method to improve their mood state and self-management ability, and further research will help provide a good solution for such patients. Mastitis is an inflammation of the breast caused by the infection that carries a risk in women of any age but is most common in lactating women . The cliThe subjects were 100 patients diagnosed with mastitis who underwent physical examination in the physical examination center of our hospital from October 2020 to October 2021. According to the order of physical examination, they were equally split into experimental group and control group. This study conformed to the Declaration of Helsinki .Inclusion criteria: (1) patients met the diagnostic criteria for mastitis, such as the hard masses with unclear boundary and poor activity, accompanied by symptoms such as redness, swelling, heat and pain, local pain of breast, and galactapostema; (2) B-ultrasonography showed irregular low-echo masses, with a few liquid echo areas occasionally; and (3) patients aged 18–60 years old and their families were familiar with the precautions of aerobic exercise.Exclusion criteria: (1) patients with organic mental disorder and mental illness; (2) patients with regular exercise habits before enrollment; and (3) patients with serious underlying diseases, such as diseases in brain, heart, liver and kidney, and hematopoietic diseases.The control group was given routine clinical intervention after diagnosis. The medical and nursing staff helped patients complete relevant examinations  and various nursing operations, eliminated their tension and fear, and ensured that they could cooperate with doctors in treatment. Any abnormalities in patients were timely reported to competent doctors. The patients were guided to face life optimistically and establish confidence in treatment , 14.The experimental group received health education combined with aerobic exercise. Health education was implemented as below. Differentiated intervention strategies and education contents were provided by the nursing staff according to the education levels, comprehension, occupation, and social status of each patient. The etiology, pathogenesis, and other in-depth medical knowledge of mastitis were illustrated to patients with a high education level, while simple and plain words were applied to those with a low education level. At the same time, patients with mastitis were instructed to master a healthy lifestyle and develop good hygienic habits. During intervention, four health lectures on disease knowledge were conducted to improve the self-management ability of patients, including healthy lifestyle, healthy exercise behaviors, correct medication, and healthy dietary behaviors.Aerobic exercise was carried out as below. According to the individual characteristics of patients, the rehabilitation physicians formulated corresponding exercise strategies. The patients carried out 2-3 times of exercise each week in the first three weeks, with the exercise time at 15–20 min each time and no intense exercise and then gradually increased the time. In the 10th week, the exercise time was increased to 35–40 min and the exercise intensity was assessed based on the patients' heart rates. Maximum heart rate = 220 − patient age. Exercise intensity was 50% of the highest heart rate in the 1–6 weeks, 60% of that in the 7–10 weeks, and 70% of that after the 10th week. The patients were guided to correctly calculate their heart rates and control the rates during exercise. Aerobic exercise included warm-up exercise, real exercise, and relaxation at a ratio of 1 : 3 : 1 in time. Various sports were chosen according to personal preferences and objective needs, such as yoga, jogging, swimming, and walking. Medical staff grouped patients according to their living areas, same interests and hobbies, and similar ages and encouraged them to engage in the same exercise and communicate with each other. At the same time, regular health education was carried out to inform patients of the benefits of adhering to aerobic exercise for the treatment of mastitis, the choice of exercise methods, and self-rescue and treatment for abnormalities in exercise. Patients were regularly followed up to ask about their exercise and physical status. The aerobic exercise was carried out for 10 weeks.The resilience scale (CD-RISC)  was adopIn terms of local situation of the affected breast, 0 point was for no local pain, 2 for mild and tolerable pain, 4 for obvious pain that did not affect sleep, and a score of 6 points was for severe local pain that seriously affected work and sleep. As for local skin condition, 0 point was for normal local skin color with no heat sensation, 2 for normal local skin color with slight heat sensation, 4 for red local skin with burning sensation, and 6 for local skin ulceration. Concerning local mass diameter, 0 point was for no local mass, 2 for a local mass diameter ≤2 cm, 4 for a local mass diameter of 2–4 cm, and 6 for a local mass diameter >4 cm.The self-management ability of patients was evaluated according to the self-designed questionnaire on self-management ability of patients with mastitis in our hospital. The questionnaire included daily life management, abnormal handling, exercise management, and self-management confidence. Each item contained five questions, and each question had five grades of positive scores (1–5 points). A higher score represented better self-management ability of the subjects.The self-made questionnaire on disease knowledge of mastitis in our hospital was used to evaluate the mastery of disease knowledge of both groups, including the pathogenesis of mastitis, treatment methods, daily nursing methods and principles, and regular return visits. The full score was 100 points, and a score ≥80 points was regarded as qualified for the mastery of mastitis-related knowledge.The MOS 36-item short-form health survey (SF-36)  was usedX2 and expressed as (n (%)), while the measurement data were tested by the t test and expressed as mean ± SD. When P < 0.05, the differences were statistically significant.The data were processed by the professional statistical software SPSS26.0 and graphed by GraphPad Prism 7 . The enumeration data were tested by P > 0.05), see No notable differences in the average age, breast feeding history, residence, family income, and other general information were observed between the two groups (P < 0.001).P < 0.001), see After intervention, the scores of breast pain, skin color, and local mass diameter in the experimental group were obviously lower than those of the control group (P < 0.001), as presented in The scores of self-management ability after intervention were notably higher in the experimental group than in the control group (P < 0.001), see The score of mastitis-related knowledge was higher in the experimental group than in the control group (P < 0.001), see After intervention, the SF-36 score was higher in the experimental group than in the control group . Clinical studies [P < 0.001), suggesting that the combined intervention greatly increases the patients' awareness of their own disease, improves their tolerance to relevant medical operations, enables them to actively cooperate with the diagnosis and treatment, and enhances their confidence in treatment. A previous study [Aerobic exercise, including the common forms of swimming, walking, skating, riding a bike, and rhythmic exercise, has always been a healthy exercise modality advocated by medical workers, already with several studies on it . This ex studies  found th studies , 24. Theus study , 26 has us study –29 has sDue to limited research conditions, this study has a short follow-up time and lacks research on the recurrence of disease after intervention. Therefore, the experimental design will be improved in the subsequent studies to provide more evidence-based proof for the clinical intervention of mastitis.


The results revealed a significant indirect effect of traumatic life events on PLEs through SD and self-reported cognitive biases. However, performance-based cognitive biases measured with three behavioral tasks were unrelated to SD and PLEs. The frequency of SD explained a substantial part (43.1%) of the variance in PLEs. Further studies with longitudinal designs and clinical samples are required to verify the predictive value of the model.Although self-disturbances (SD) are considered to be a core psychopathological feature of schizophrenia spectrum disorders, there is still insufficient empirical data on the mechanisms underlying these anomalous self-experiences. The aim of the present study was to test a hypothesized model in which cognitive biases and exposure to traumatic life events are related to the frequency of SD which, in turn, contribute to the frequency of psychotic-like experiences (PLEs). Our sample consisted of 193 Polish young adults from the general population  who experience frequent PLEs. Participants were interviewed for PLEs, SD and social functioning as well as completed self-reported questionnaires and behavioral tasks that measure cognitive biases . The model was tested using path analysis with structural equation modeling. All of the hypothesized relationships were statistically significant and our model fit the data well [χ Phenomenological analyses along with empirical studies suggest that self-disturbances (SD), which are anomalous experiences of basic sense of self, are the core psychopathological feature and phenotypic trait marker of schizophrenia spectrum disorders –6. SD reDespite SD great importance to the conceptualization of psychosis, there is still insufficient empirical data on the mechanisms underlying these experiences. Recent studies have shown , 17 thatprimary or secondary in nature. Primary SD reflect disturbances in early neurodevelopment, whereas secondary SD appear later as defensive-compensatory reactions to other factors such as childhood adversities, social stress and marginalization. Haug et al.  . The PQ-To evaluate PLEs for their clinical relevance in the second stage of the study we used the Comprehensive Assessment of At-Risk Mental States (CAARMS) , for theTo evaluate SD we used the SQUEASE . This is a short version of the Examination of Anomalous Self-Experience (EASE), which is a semi-structured phenomenological interview developed by Parnas et al.  to examiChildhood Experiences of Care and Abuse Questionnaire (CECA.Q)  was usedSocial and Occupational Functioning Assessment Scale (SOFAS)  is a oneThe Davos Assessment of Cognitive Biases Scale (DACOBS) , for theThree computer-based tasks were used to assess different cognitive biases:Overperceptualization bias was measured with a computer-based task of auditory false perceptions—Overperceptualization Task . The AMT is a computer-based task  of the latent variable of self-report cognitive biases to verify the original structure of this measure. For performance-based cognitive biases, we aimed to build a factorial model consisting of the results of three tasks: Action Memory, Overperceptualization and Fish Task. PLEs, SD and exposure to traumatic life events were represented in our model by single indicator variables. This decision was dictated by the absence of an established factorial model for positive symptoms in CAARMS, SQUEASE and CECA.Q measures. It also enabled conserving free parameters and increased stability of the parameter estimates for the models.In the next step, we evaluated hypothesized associations with the structural equation model (SEM) in a series of path analyses to test our theoretical model. Therefore, we tested for the indirect effect of traumatic life events through SD and cognitive biases to PLEs. For this purpose, we used the bootstrap method as recommended by Preacher and Hayes . Due to n = 2,000) procedure of correction for non-normal distribution. We verified goodness of model fit following the guidelines from literature  were estimated with the maximum likelihood estimation procedure with the Bollen-Stine bootstrap . SD correlated significantly also with self-report cognitive biases and psychological abuse from the father. Except for physical and sexual abuse, all other types of traumatic life events significantly correlated with self-report cognitive biases. It is of note that no subscale of CECA.Q was significantly related to PLEs. These statistically significant relationships among variables of interest allowed for further testing of our hypothesized model with SEM. Surprisingly, no significant relationships were found between performance-based cognitive biases and SD as well as PLEs, thus planned path analysis with these variables was not performed. Furthermore, we found a highly significant correlation between self-report cognitive biases and PLEs. Thus, we decided to investigate an additional model including this path. Gender was not included in path analyses as it was not significantly related to exposure to trauma and other variables of interest. Age significantly correlated with SD , PLEs  and cognitive biases . However, those paths turned out to be insignificant thus we did not include them in the final analyses.p > 0.05; RMSEA = 0.00 (90% CI = 0.000–0.037), CFI = 1.00, TLI = 1.023, SRMR = 0.014]. For PLEs, SD and traumatic life events, we used single indicator variables, which was the sum of the frequency and severity scales obtained for all items in the positive symptoms subscale of CAARMS and in father psychological abuse subscale of CECA.Q. In the case of SD we used only the sum of the frequency scale, as the level of presence is a qualitative scale.Due to the inability to confirm the original latent structure of the 42-item DACOBS questionnaire measuring cognitive biases, we decided to use as indicator variables the sum of the points obtained in each subscale instead of all single items. We removed only jumping to conclusion subscale because of its insignificant loading. Thus, the final latent structure for self-report cognitive biases consisted of six indicators  and fit the data well . However, the path from father psychological abuse to SD turned out to be insignificant. A detailed model is presented in the Results of first path analysis suggested a model that fit the data well [χ2 (23) = 33.780, p = 0.001). This model explained 39.6% of the variance in PLEs. All of the model fit indices were satisfactory: χ2(24) = 40.847; p = 0.017; RMSEA = 0.060 (90% CI = 0.025–0.091), CFI = 0.968, SRMR = 0.059, TLI = 0.953.The first model with initially hypothesized relationships is depicted with its standardized path coefficients (standardized regression weights) in p = 0.001). The percentage of the variance explained in PLEs was equal to 43.1%. The model has a good fit: χ2(23) = 31.201; p = 0.118; RMSEA = 0.043 (90% CI = 0.00–0.078), CFI = 0.985, SRMR = 0.041, TLI = 0.976.The second model includes an additional path from self-report cognitive biases to PLEs and is presented in In the current study, we focused on the relationship between SD and PLEs with exposure to traumatic life events and cognitive biases as potential mechanisms underlying SD. All of the hypothesized associations were found to be statistically significant and the model fit the data well. SD along with its postulated mechanisms explained a substantial part of the variance in PLEs, pointing to the importance of this construct in elucidating and understanding psychosis risk. Results of our study, although obtained in a non-clinical sample, are in line with the basic-self-disorder model of schizophrenia , 55.Several points should be noted regarding the results of our study. First, we found a statistically significant indirect effect of trauma on PLEs, which is consistent with many theoretical and empirical accounts on the role of trauma in shaping psychosis risk –59. Howesecondary diminished self-presence, one of the aspects of SD, that could be the result of defensive—and in this sense secondary—dissociative reactions to traumatic situations  and in relation to specific perceptual material. Therefore, performance in behavioral tasks may be more influenced by immediate context and affective state for example, whether the person is feeling stressed, relaxed, distracted at the time of testing. This discrepancy between self-report measures and objective neuropsychological results has been observed in previous studies (The role of the second possible mechanism of SD—cognitive biases—is somewhat more difficult to interpret. Although self-report cognitive distortions showed an association between trauma and PLEs, this was not the case for  studies , 73. AnoIt is worth noting that although we hypothesized cognitive biases affect PLEs solely through SD, correlation analysis clearly indicated a highly significant direct relationship between cognitive biases and PLEs. Path analyses suggest that although there is an indirect effect of trauma on PLEs, our results suggest cognitive biases also make a direct and unique contribution to PLEs that goes beyond the presence of SD. This is in line with a cognitive model of psychosis , 74 whicOur model may have clinical implications. Different risk factors such as a history of exposure to trauma, cognitive biases and SD should be considered jointly in screening procedures to maximize chances for identifying people who are at the highest risk for psychosis. As SD was the variable that had the highest regression coefficient with PLEs, particular attention should be paid to identify these anomalous self-experiences when detecting individuals at risk and preventing the development of full-blown psychosis . CognitiThe results of the study should be interpreted in light of its strengths and limitations. The strengths of the study lie in the combination of different levels of measures, namely self-report, clinical interviews and behavioral tasks. To the best of our knowledge, this is the first study simultaneously examining trauma exposure and different types of cognitive biases and their relation to SD and PLEs in a non-clinical sample. However, the cross-sectional design of the study precludes causal inference. Therefore, future longitudinal studies in clinical samples are needed to address causality and capture the change in SD and PLEs over time. Further validation of our model should be carried out using the full version for the clinical interview of SD, the EASE . This woThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the ethics committee of the Medical University of Warsaw, Poland. The patients/participants provided their written informed consent to participate in this study.ŁG and RP-U: conceptualization and writing. RP-U: data curation, formal analysis, roles/writing—original draft, and visualization. ŁG: funding acquisition. RP-U, AC, DF, and ŁG: investigation. ŁG, DF, and AC: methodology, project administration, resources, and software. LG: supervision. All authors review & editing.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.