To determine prognostic factors for patients with uveal melanoma without metastases and to construct nomograms to predict their 3- and 5-year overall survival (OS) and cancer-specific survival (CSS).  We included 4119 patients who were registered from 2004 to 2015 in the Surveillance, Epidemiology, and End Results database. The median follow-up time was 5.8 years. Independent risk factors affecting OS and CSS were identified with univariate and multivariate Cox regression analyses and used to construct nomograms. Internal and external validation were carried out by using the bootstrap method to calculate the concordance indices (C-indices) and plot the calibration curves.  Age, primary site, histological type, T-stage, and treatment were independent risk factors for OS and CSS; marital status and sequence number were factors only for OS. The C-indices for internal validation of OS and CSS were 0.713  and 0.708 , respectively, and for external validation they were 0.729  and 0.731 , respectively. The calibration curves also revealed good agreement between the predicted and actual survival rates.  We constructed nomograms to predict the 3- and 5-year OS and CSS of patients with uveal melanoma without metastases. Our nomograms may improve prognostication and assist with the development of individualized treatment strategies. Uveal melanoma (UM) is a common primary intraocular malignancy in adults, mainly originating from pigment and nevus cells within the uveal tissue. UM can be divided into choroidal, ciliary-body, and iris melanoma, with choroidal melanoma accounting for 86.3% of UM cases . The repUM is highly malignant and prone to metastasis, with the liver being the most common site of metastasis . Due to Currently, the prognosis of uveal melanoma can be predicted by several independent factors without the use of an ideal prognostic prediction model. Moreover, we are aware of no reports on prognostic factors and survival rates of patients with UM without metastases. Nomograms are used as simple statistical tools for the accurate prediction of patient prognoses, with visualized results, with the aim of improving patient outcomes. The Surveillance, Epidemiology, and End Results (SEER) database is the most authoritative source of information on cancer incidence and survival in the United States, covering approximately 28% of the population in 18 different population groups . In this∗Stat software (seer.cancer.gov/seerstat) version 8.3.9. The site codes for the choroid (C69.3) and the ciliary body and iris (C69.4), as well as several International Classification of Diseases for Oncology codes  were used to identify patients with UM. We collected data from 5545 patients who were diagnosed with UM from 2004 to 2015 in the SEER database. We excluded 354 patients with metastases. Further exclusion criteria were as follows: unknown marital status, unknown race, unknown laterality, unknown T-stage, and unknown treatment. Finally, 4119 patients were included in the study, of which we allocated 2883 to the training group and 1236 to the validation group, in a ratio of 7 : 3  staging system, as the 7th edition was only published in 2010. The primary endpoints were OS and CSS. OS was defined as the time from diagnosis to death or the end of follow-up and CSS as the time from diagnosis to UM-related death or the end of follow-up.P < 0.05 were included in the multivariate Cox regression analysis for determination of the independent risk factors affecting the OS and CSS.The optimal cut-off values for age (57 and 79 years) were determined by using X-tile software, thus dividing the patients into three age groups: ≤57 years, 58–79 years, and ≥80 years. We performed statistical analysis by using IBM SPSS Statistics for Windows version 26.0 . Group allocation was performed by using the random case selection method in a ratio of 7 : 3 for training : validation. We described the numbers and percentages of cases for each baseline characteristic in the overall, training, and validation groups and compared the statistical differences between the training and validation groups by using the chi-square test. The hazard ratios (HRs) and 95% confidence interval (CI) were calculated by using univariate and multivariate Cox regression analyses. The potential risk factors in the training group were determined by using a univariate Cox regression model, and the variables with P-values in this study were two-tailed, and differences were considered statistically significant when P < 0.05.We used R software 4.0.5  to incorporate the independent risk factors from the multivariate Cox regression analyses into nomograms for the prediction of the 3- and 5-year OS and CSS values for patients with UM without metastases. Internal and external validation of the constructed nomograms were carried out by using the bootstrap method to calculate the concordance indices (C-indices) and plot the calibration curves. The C-index can be used to evaluate the predictive ability of the model. A value of 0.5 indicates that the model is not predictive, values from 0.51 to 0.70 indicate low predictive accuracy, values from 0.71 to 0.90 indicate moderate predictive accuracy, and values above 0.90 indicate high predictive accuracy. All P > 0.05)  . RegardiP < 0.05). In addition, sequence number was associated with OS (P < 0.05). To exclude the effect of confounding factors, the significant factors were included in a multivariate Cox regression analysis (P < 0.05), and five factors  were associated with CSS (P < 0.05).Among the 4119 patients with UM without distant metastases, 1563 patients died during the study period, of which 920 died because of UM, yielding 3- and 5-year OS rates of 83.3% and 73.0%, respectively, and 3- and 5-year CSS rates of 88.5% and 81.8%, respectively. All the possible prognostic factors were included into the univariate Cox regression analysis of the training group . As a reanalysis . As a reThe constructed nomograms Figures  and 3 arWith the bootstrap method in this study, we performed 1000 resamples and obtained C-indices of 0.713  and 0.708 , respectively, for the nomograms used to predict OS and CSS during internal validation, and 0.729  and 0.731 , respectively, during external validation. We plotted the calibration curves of the internal and external validations Figures  and 5, wMelanoma is a highly malignant cancer of melanocytic origin that can arise from multiple primary sites, such as the skin, mucosa , and eyes . About 5% of melanomas originate in the eye, and of those, about 85% originate in the uvea . Up to 5In this study, 4119 patients with UM without metastases who were registered in the SEER database were included. After univariate and multivariate Cox regression analyses, we constructed nomograms for the prediction of patients' 3- and 5-year OS and CSS. The evaluation and validation of nomograms may be internal or external. Internal validation is the validation based on the data in the training group, which is part of the model construction; its main purpose is to verify the repeatability of the prediction model and prevent the overfitting of the model. External validation is the application of the constructed prediction model to the validation group; this process includes the calculation of the predicted values for comparison with the actual values to assess whether the prediction results of the prediction model are reliable. Internal and external validation revealed good agreement between the predicted and actual survival rates, indicating that these nomograms are accurate tools for the prediction of survival rates.P-value was exactly 0.05, which was the threshold value selected in this study. The impact of sex on the survival of patients with UM is controversial. Some studies have demonstrated that sex is not associated with the prognosis of patients with UM [UM is most often observed in patients of advanced age. We demonstrated that higher age was associated with lower survival rates. This may be due to the fact that younger patients have a higher proportion of iris melanoma, which is more likely to be far from the central macula and optic disc, with smaller tumor diameter and thickness, and a lower chance of tumor spread compared to other types of UM, while older patients have poorer underlying conditions and more complications . The uni with UM , while i with UM . Marital with UM . In this with UM . Patient with UM . The fin with UM .The vast majority of patients with UM have monocular disease; in this study, there were only three cases of bilateral disease. We observed no statistically significant difference in the survival rates between monocular and bilateral disease, which is consistent with the findings of previous studies . As for Tumor stage is an important marker of prognosis, as there were few patients with stage T4 UM without metastasis; we combined patients with stage T3 and those with stage T4 tumors into one group for analysis. We observed that the survival rate gradually decreased with an increase in T-stage. Previous studies demonstrate that the average age of diagnosis gradually increases as T-stage increases, as does the tumor thickness, tumor diameter, and the risks of subretinal fluid, Bruch's membrane rupture, and extraocular spread .The main treatment options for UM are surgery and radiation. Surgical treatment includes enucleation and local excision. Enucleation is the traditional method, although it is no longer the first choice for treating UM because the distant metastasis of the tumor may be accelerated by the pulling and squeezing of the vascular tissue during surgery . As loca“Multiple primary cancers” refers to the simultaneous or sequential occurrence of two or more independent primary malignancies. In our study, the majority of patients had single primary cancers, and they had a better OS than patients with multiple primary cancers. We concluded that the sequence number did not affect the CSS, as most patients with multiple primary cancers died because of other secondary tumors or systemic diseases. Previous studies have shown that patients with UM have a 9% increased risk of developing a second malignancy, such as cutaneous melanoma, leukemia, thyroid cancer, kidney tumors, and tumors of other parts of the eye or orbit, compared to healthy individuals. On the other hand, there was an 8% increased risk of developing UM after the first diagnosis of any of these other tumors .The present study is subject to certain limitations. First, the results would be more convincing if the prediction model were validated in a multicenter study with large-scale data from other databases or research centers. We are conducting research in our own hospital to verify the findings of this article, and the results will be presented in our next article. Second, some important prognostic indicators are not included in the SEER database, such as tumor thickness, mitotic activity, degree of lymphocyte infiltration, karyotype, and gene expression profile. Finally, there were missing data for some patients regarding the specific histological type. However, if we removed these patients from analyses, the number of cases would be reduced substantially, lowering the accuracy of the results. Despite these limitations, we believe that the prognostic nomograms are useful for the prediction of individual survival rates for patients with UM without metastases.Advanced age, ciliary-body involvement, epithelioid-cell melanoma, more advanced T-stage, and surgery-only treatment are independent risk factors for both a poor OS and a poor CSS in patients with UM without metastasis. Widowhood and multiple primary cancers are independent risk factors only for OS. We constructed nomograms to predict the 3- and 5-year OS and CSS, providing a potentially more accurate and individualized method to predict patient survival. These nomograms may ultimately serve as a basis for the development of individualized treatment strategies.


Rates of mental health issues have been increasing among university students. This study investigates the effects of the Interculturality and Mindfulness Program (PIM) on academic students on mindfulness, emotional regulation, depression, anxiety, stress, life satisfaction, optimism, positive solitude, and loneliness. A quasi-experimental research was conducted, with pre- and post-test comparative measurements in three groups: in-person (IG), synchronous online (OG), and passive control (CG). A diverse group of students  participated from two universities in Portugal. When compared to the CG, both active groups (IG and OG) demonstrated a beneficial interaction effect in acceptance, positive solitude, optimism, and mindfulness. The IG demonstrated a positive interaction effect in awareness and satisfaction with life, whereas the OG indicated a favorable interaction effect in impulse. When analyzing the intra-group effects, both active groups presented a significant improvement in stress, emotion regulation, mindfulness, positive solitude, and optimism. The OG demonstrated an improvement in awareness and loneliness. The main limitations of this research are that students were not randomly assigned, and groups were heterogeneous in nationality, education level, and sex. Nonetheless, PIM has indicated beneficial results in both IG and OG, and is a promising intervention for the prevention of mental health issues , as well as for the promotion of well-being . University students’ psychological stress is increasing in terms of severity and prevalence and has become a public health concern due to the negative effects on personal development and academic performance . The WorMental issues, if not receiving the necessary attention, in addition to affecting student’s performance, can lead to academic dropout. Respondek et al.  analyzedOne of the factors that tends to increase anxiety in university students is the adaptation to the new context. Undergraduates encounter a social challenge as they enter a new environment and interact with a greater diversity of cultures. The University of Algarve , for instance, receives students from 86 different nationalities, with 25% of the student population comprising foreign students . In addiIn order to promote social integration, interventions based on cross-cultural psychology may be valuable. Cross-cultural psychology is “the study of similarities and differences in individual psychological functioning in various cultural and ethnocultural groups” . By acquIn contrast, many studies with mindfulness-based interventions (MBIs) have been published as an alternative to promoting mental health, such as well-being and emotion regulation, among university students, and have demonstrated promising outcomes ,14. MindAs the implementation of group interventions seems to be a suitable initiative to promote mental health in the university setting, the Interculturality and Mindfulness Program (PIM) was developed in 2018 [The present study used a quasi-experimental design, with pre- and post-test comparative measurements in three groups: in-person (IG), online (OG), and control (CG) .University students regularly enrolled in different courses at UAlg, located in the south of Portugal, participated in the in-person and online programs, whereas students from the University of Beja joined the control group. In total, the three groups consisted of 150 participants, with a mean age of 25.4 . Considering the participants who completed the pre- and post-test, 70  belonged to the IG, 44  were from the OG, and 36  students were from the CG. Participants’ courses totalled 39, and the most frequent were: Management , Psychology , Water and Coast Management , Biomedical Sciences , and Computer Engineering . Participants’ socio-demographic data demonstrate homogeneity in age in the three groups, but shows heterogeneity in gender, education level, and nationality. The CG had significantly fewer women (69.4%) than the IG (74.3%) and the OG (90.9%); whereas the IG had fewer Portuguese students (25.7%) compared to the OG (75%) and the CG (83.3%). Even though most participants were undergraduates in the three groups, IG had significatively more doctorates than the OG and the CG, whereas the OG showed a higher percentage of master students than the IG and the CG.Sociodemographic questionnaire. Developed by the authors. This is a brief form containing questions regarding participant’s sociodemographic data, as well as health and psychological conditions to certify if the program is suitable for him/her.Difficulties in Emotion Regulation Scale (DERS). Developed by Gratz and Roemer [d Roemer  and trand Roemer . It assed Roemer . In the Depression, Anxiety and Stress Scale (DASS-21). Developed by Lovibond and Lovibond [Lovibond  and tranLovibond . DASS-21Loneliness and Positive Solitude Scale (LPSS). Developed by Chiodelli et al. [i et al. , this scPhiladelphia Mindfulness Scale (PHLMS). Developed by Cardaciotto et al. [o et al. , validato et al. . It consFreiburg Mindfulness Inventory (FMI). Short Version by Walach et al. [h et al.  was tranh et al. . This inSatisfaction with Life Scale (SWLS). Developed by Diener et al. [r et al. , to asser et al. , and theOptimism Scale. Developed by Oliveira [Oliveira  for the Students were invited to participate through the University’s institutional e-mail, posters, and social media. Two weeks in advance of the first session, facilitators offered a PIM presentation workshop (session zero). In session 1, participants were required to complete and sign the free and informed consent form.In the IG, sessions were held in a spacious classroom at the University, with chairs arranged in a circle. Screen projections and a whiteboard were used as a support for the proposed activities. The OG was synchronous, conducted through Zoom video conference platform, and had the same duration as the IG. Activities which involved more physical interactions had to be adapted when transposing from IG to OG. However, the activities’ main intentions were not modified. The CG was a wait-list group for the Soft Skills for Life Program  from theSix PIMs’ editions were applied in the face-to face format (IG) between April 2018 to December 2019, whereas four were held via videoconference (OG) and occurred between April and December 2020. The CG was conducted between February and March 2021. Students’ adherence from both intervention formats are shown in The Interculturality and Mindfulness program (PIM) was developed and facilitated by_Roberto Chiodelli, Diana Fernandes de Oliveira, and Luana Thereza Nesi de Mello, all Psychology doctoral students under the supervision of Saúl Neves de Jesus. Roberto Chiodelli is a psychologist, with a M.S. in Clinical Psychology, and a facilitator of the Mindfulness Protocol Body in Mind Training . Diana FPIM consisted of six weekly sessions lasting two hours each see . At the Activities and content from the perspective of interculturality were based on an array of works in this field ,37,38. MPsychometric tests were applied in the first and in the last (sixth) session. Whereas these instruments were answered via paper and pen in the IG, the psychometric tests, informed consent form, as well as the data protection term were completed via Google Forms in the OG. Students from the CG also filled the survey via Google Forms.The statistical data treatment was performed with the aid of the software Statistical Package for Social Sciences version 25.0 for Windows, with a 5% significance level. Results were presented using descriptive statistics through absolute and relative distributions (n/%), as well as through the mean and standard deviation, with the study of symmetry using the Kolmogorov–Smirnov test.Effect analysis on the groups was performed using generalized estimating equation models, a linear model, followed by Bonferroni’s multiple comparisons test. Impact identification in each group was investigated by estimating Cohen’s d effect size.t-test was applied when comparing two independent groups.For analysis involving the intra-group variables comparison, the generalized estimating equations (GEE) with post hoc Bonferroni was utilized. In the comparison of continuous variables between groups, the one-way variance analysis with post hoc Sheffé was used. The Student’s Regarding the categorical variable comparisons between groups, Pearson’s chi-square test was used, as well as Fisher’s exact test (Monte Carlo simulation). The Cochran Q test was utilized when this analysis occurred intra-group (dependent data).p = 0.017). In addition, goals (DERS) dimension was significantly lower in T1 for the CG when compared to IG and OG (p = 0.016). Lastly, the awareness (DERS) baseline mean was higher in CG when associated with the two other groups (p ≤ 0.001). Generalized estimating equation (GEE) models’ data of each variable over the three groups pre- and post-intervention are found in p = 0.002), where IG  showed a significant growth over time, whereas OG (p = 0.168) and CG (p = 0.502) means remained unchanged. All interaction effects were in a positive direction.These findings demonstrate that, compared to the passive control group, both in-person (IG) and online (OG) PIM had a positive impact on most variables analyzed. In general, IG and OG were equivalent in terms of their effects. IG presented two specific dimensions of interaction effect (Awareness (PHMLS) and Satisfaction with Life (SWLS)) versus one for the OG (Impulse (DERS)). On the other hand, OG had three specific intra-group beneficial effects (Impulse (DERS), Awareness (DERS), and Loneliness (LPSS)), versus two of the IG (Awareness (PHMLS) and Satisfaction with Life (SWLS)). A more detailed comparative analysis between the IG and OG was performed in the study which examines PIM effects in three different times  .Anxiety (DASS-21) and depression (DASS-21) are the variables that did not demonstrate significant effects in any group. Although some research with MBIs among university students demonstrates significant reductions in depression and anxiety ,43, otheAs found in other investigations ,47, therMindfulness skills have a direct relationship with emotion regulation , which iWhen analyzing the intra-group results of both PIM formats, all DERS subscales presented a significant reduction in at least one of the groups. Impulse had a significant interaction effect for the OG, which denotes that the online intervention more sharply reduced the difficulty of remaining in control of participant’s behavior when experiencing negative emotions, when compared to the other groups. The OG also showed an intra-group reduction in awareness (DERS), which has a more specific meaning than the PHMLS variable of the same name. It refers to a lack of awareness or attention to emotional responses, whereas the PHMLS dimension involves external awareness, thoughts, bodily sensation, as well as emotions. The variables Strategy (belief that there is little one can do to regulate oneself once upset), Clarity , and Non-acceptance (tendency to have a negative secondary or non-accepting reaction to one’s own distress) decreased in both OG and IG. Lastly, the goals dimension, which means the difficulty in concentrating and/or accomplishing tasks when experiencing negative emotions, showed a reduction in the OG and, interestingly, in the CG, being the only variable with a significant change in the passive group.An interaction effect for Positive Solitude was found in both active groups. This construct can be defined as a voluntary aloneness, during which personality development and creativity may emerge. In this state, the individual enjoys the experience of spending solitary time and can use it to explore himself/herself. He/she is not avoiding social interaction due to social anxiety or preference ,51. BasiStress reduction in both active groups is relevant, but expected when examining the MBI literature. Lovibond and Lovibond  define sOptimism also showed a significant interaction effect in the two active groups when compared to the passive one. This dimension can be defined as an emotional and cognitive predisposition to think and react to others and events in a favorable way, instead of expecting harmful outcomes . NumerouSatisfaction with life, another positive dimension, had a significant interaction effect in the IG. This variable refers to the cognitive component of subjective well-being, in which individuals globally assess the quality of their lives based on their own criteria . By the In addition to mindfulness, intercultural-based dynamics had an important impact on the participants’ journey along PIM. These activities fostered a sharing of experiences among students based on the topic of cultural diversity, to provide greater group cohesion, which is a key component for all groups . ParticiWhen analyzing student’s adherence , it is nSome limitations are detected in this study and should be considered. Although groups were homogeneous in age, they were heterogeneous in terms of gender, education level, and nationality. The nationality difference was since the first IGs were more publicized to international students. Moreover, group application occurred at different times. Furthermore, COVID-19 affected everyone and should also be taken into consideration. Another limitation is that participants were not randomly allocated to the three groups, which would offer greater reliability to the results. Finally, the applied measures were self-reported. The use of biological or behavioral measures would offer more robust evidence.In spite of its limitations, this study provides evidence that confirms results of similar interventions and reinforces the importance of programs to be implemented in the academic environment. PIM has proved to be relevant and very promising both for the prevention of mental health problems  and for the promotion of well-being . Such benefits tend to promote a higher engagement of the student in the university context and, consequently, reduce academic dropout. We hope PIM can be replicated in future studies.


Social media addiction has been a hot issue in scientific research in recent years, its antecedents and consequences have been extensively studied. Among these studies, Bergen Social Media Addiction Scale (BSMAS) is one of the most commonly used instruments. However, little is known about whether this scale has the equivalent psychometric properties for men and women. The purpose of the current study is to examine the measurement invariance  of the BSMAS across genders. In total, 1,120 participants were recruited from 5 universities. R program was applied to conduct the single-group and multiple-group confirmatory factor analysis (CFA) based on the social media addiction symptom ratings. The results demonstrated that BSMAS was a valid and psychometrically robust instrument for assessing the risk of social media addiction among university students, and that the four types of measurement invariance of the BSMAS across genders were confirmed. Consequently, gender differences in the BSMAS scores are likely to reflect the genuine differences between men and women, and comparisons on the level of social media addiction of university students between gender groups can be interpreted meaningfully. Social media has brought great convenience to our daily life. It integrates many interesting and useful functions such as instant messaging, games, music, short video, and so on. These services not only allow individuals to connect with others irrespective of the constraints of time and space; but also provide numerous leisure activities, and make life rich and colorful. Therefore, many people tend to spend lots of time on social media, under this circumstance, they may be very likely to develop the problematic behavior–social media addiction. Social media addiction refers to the behavior characterized by being excessively concerned about social media activities and spending too much time and effort on these activities, at last, the work, study, interpersonal relationship relationships, mental health, and other important life areas were impaired  was administered to assess the level of one's social media addiction. Participants were asked to report their experiences in the use of social media within a 12-month period. The BSMAS consisted of 6 items , each item reflected one of the core addiction components  proposed by Griffiths . Before sending out the questionnaires, all the participants were informed that the data were only used to conduct scientific research, they were not compelled to participate in the study; their responses were anonymous; they could drop out at any moment they would like and this would not impact their life and their performance in the final examination. Finally, after acquiring the informed consent of the participants and their teachers or supervisors, questionnaires were merely distributed to the students who were willing to participate in this study.2 statistic, Root Mean Square Error of Approximation (RMSEA), Comparative Fit Index (CFI) and Standardized Root Mean Square Residual (SRMR). For RMSEA, a value smaller than 0.05 represented a close fit; a value ranging from 0.07 to 0.08 indicated a fair fit; a value in the range of 0.08 to 0.10 denoted a mediocre fit , CFI = 0.994, SRMR = 0.018, the standardized factor loadings ranged from 0.637 to 0.753. In the male sample, fit indices of CFA suggested the model was appropriate: χ2 = 10.837, RMSEA = 0.020 , CFI = 0.999, SRMR = 0.013, the standardized factor loadings ranged from 0.653 to 0.770. In the female sample, the outcomes also showed an acceptable model fit: χ2 = 51.820, RMSEA = 0.089 , CFI = 0.983, SRMR = 0.030, the standardized factor loadings ranged from 0.629 to 0.735. In summary, results of CFA indicated the unidimensional model of BSMAS was acceptable for both gender groups.Single-group CFA was conducted for the overall sample and individually for each gender. The unidimensional model was tested in the overall sample, male and female groups separately. Results of single-group CFA in the overall sample and each subsample were presented in Multiple-group CFA was performed to examine the measurement invariance across genders. Fit indices for the four models and the differences between the pairs of nested models were displayed in 2 = 64.947, RMSEA = 0.068 , CFI = 0.991, SRMR = 0.023). Therefore, the configural invariance of the BSMAS was confirmed.First, configural invariance was conducted by estimating the two gender groups with no equality constraint. The results indicated the configural invariance model (M1) fit the data well , CFI (ΔCFI), and SRMR (ΔSRMR) were −0.026 < 0.050, 0.002 < 0.004, −0.001 < 0.01, respectively, this indicated that the metric invariance of the BSMAS held across genders.Second, metric invariance was performed through constraining the factor loadings to be the same between male and female groups. The fit indices suggested an acceptable model fit. Compared with M1, the metric invariance model (M2), Δχ2 = 71.020, RMSEA = 0.037 , CFI = 0.994, SRMR = 0.023). Compared with M2, the values of ΔRMSEA, ΔCFI, and ΔSRMR were all smaller than the recommended cutoff values for rejecting measurement invariance. The satisfaction of scalar invariance implied that the factor loadings and item intercepts were invariant for men and women.Third, scalar invariance was evaluated by restricting the factor loadings and intercepts of the items to be equal across the two gender groups. The results of the scalar invariance model (M3) demonstrated that the model fitted the data well , CFI = 0.995, SRMR = 0.023). Compared with M3, the values of ΔRMSEA, ΔCFI, and ΔSRMR were all within the recommended guidelines for supporting the strict invariance. Therefore, the strict invariance of the BSMAS across genders was confirmed.Forth, strict invariance estimated through forcing the factor loadings, intercepts, and residual variances of the items to be the same across genders. The strict invariance model (M4) provided satisfactory fit indices  of the BSMAS also suggested that the psychometric properties of this instrument were equivalent in both male and female groups. The same scores of the BSMAS reflected the identical severity of social media addiction across genders, and this might not be affected by the artifacts of measurement bias. Therefore, in Chinese college student populations, it is acceptable to use the BSMAS to compare the levels of social media addiction in different genders. This conclusion was similar to one previous study in which primary school students were enrolled as the participants  Inner Mongolia Normal University graduate students' research innovation fund (CXJJB20004). (2) Social Science Planning Project in Inner Mongolia, Evaluation System and Intervention Research of Adolescent Health Literacy in Inner Mongolia under Healthy China Strategy (2021NDB130). (3) Baotou Medical College's research project of Wen Xue, Wei Xue and Jian Xue, a study on emotional adjustment strategies and influencing factors of college students under the influence of public emergencies (2021BYWWJ-YB-37). (4) Inner Mongolia Natural Science Foundation, Exercise improves executive function in patients with chronic pain (2021MS03099).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.


This study aimed to compare compliance between pediatric patients with amblyopia undergoing a smartphone virtual reality-based training method (EYEBIT) and those receiving traditional patching method training.n = 76) were randomized into the traditional patching and EYEBIT training method groups. The patients received training methods once a day for 2 h and 1 h in the patching and EYEBIT groups, respectively. Follow-up assessments involved interviews with parents regarding children's compliance and questionnaire-based interviews with children; compliance rating was compared between the methods.A crossover design was adopted in this study. The enrolled children (p < 0.05). The EYEBIT method was associated with better compliance than the traditional patching method. Significant correlations were observed among compliance components in both methods. In the correlation analysis between the two groups, the research results showed that in the EYEBIT group, the correlation between children's compliance behaviors and children's compliance attitudes, the correlation between children's compliance behaviors and parents' compliance behaviors, and the correlations between children's compliance attitudes and parents' compliance attitudes were all negatively correlated, and in the traditional patching group, the above three correlation analysis results were all positive.All children completed the training and follow-up assessments. There were significant differences in parent and children compliance-related behavior and attitudes between the two training methods (The use of the EYEBIT method may improve compliance in children with amblyopia; this method appears acceptable to the parents of children with amblyopia. Amblyopia is a common eye disease in children associated with impairments in processing tactile, motion, and visual stimuli, resulting in abnormal visual development, low visual acuity, and binocular diplopia –3. AmblyTreatment choices depend on children's age, visual acuity, compliance, and response to previous treatment, as well as children's physical, social, and psychological development. Treatment methods include refractive correction, traditional patching, atropine fogging, filter, optical fogging, and dichoptic training –8. The pA growing body of research has exposed the limitations of these treatment methods . TraditiMezad-Koursh et al.  used theBased on previous research, we adopted the EYEBIT mobile phone software system developed by Gang at the Schepens Eye Research Institute of Harvard Medical School, combined with virtual reality technology, for training patients with pediatric amblyopia. This approach was used to eliminate the shortcomings of approaches previously used in China and elsewhere for dichoptic training to treat amblyopia. To support future studies, this study aimed to evaluate compliance rates associated with this training system.EYEBIT consists of five modules.Video playback module: (1) Play local video; (2) Switch videos in virtual reality environment; (3) To realize the simultaneous training method for amblyopia treatment, different sizes of central covering areas can be set in both eyes; (4) In the virtual reality environment, the two windows can move in the same direction or in the opposite direction to achieve the function of training fusion.Screen sharing module: (1) To realize the screen sharing function between mobile phones, parents can observe the image situation of children's training through the shared mobile phone; (2) Research physicians or family members can control the images and training time of children through sharing mobile phones.Parameter control module: (1) Unified management of all user parameters, can achieve global access; (2) It can read and write files in a fixed format to realize the function of reading the parameters of the treatment plan sent remotely by doctors; (3) parameter format control.Head movement detection module: it can recognize simple head movement posture, such as turning head left, turning head right, raising head, and lowering head, to flexibly control the picture and switch the video during training.Server management module: (1) Upload valid user training duration; (2) Upload masks with different degrees of ambiguity used by users in different times of training.EYEBIT is a mobile app that plays a video stream in two windows on the phone screen to allow the video to be watched through a pair of virtual reality goggles . For ambMost children with amblyopia have reduced binocular fusion function; thus, the EYEBIT system was designed to shift the two viewing windows toward and away from each other. The amount and frequency of shift were set according to patients' fusion function. The shift was specified in prism diopter  and the frequency of shift in times/minutes . Thus, during the amblyopia training, the patients also underwent fusion training , which mUsing EYEBIT, patients were able to select the videos for their training according to their personal preferences. The viewing distance, magnification, fusion change step, and interpupillary distance were set by clinicians.The study was approved by the hospital ethics committee (K2018-12-031). Children aged 4–14 years who were diagnosed by an ophthalmologist as having anisometropic amblyopia, refractive amblyopia, deprivation amblyopia, and strabismic amblyopia were screened. Visual acuity was examined according to the international standard visual acuity chart; the best-corrected visual acuity of the amblyopic eye was 0.1–0.5, and that of the dominant eye was higher than or equal to 0.8 ; the difference in best-corrected visual acuity values between the two eyes was more than two lines in the standard logarithmic visual acuity chart. For strabismic amblyopia, the degree of strabismus was ≤ 5 PD after optical correction or surgical treatment. Children were eligible for this study provided that their parents were willing to consent to study participation and cooperate with study activities, including follow-up assessments.Among children with amblyopia, those with major systemic hereditary diseases  were excluded; those with other ocular organic diseases, e.g., congenital cataract, congenital glaucoma, and corneal diseases, were excluded; children with a history of atropine treatment for amblyopia, gestational age at birth of <32 weeks, or birth weight of <1.5 kg were excluded.All patients were instructed to take 2-h traditional patching therapy and also 1-h EYEBIT training every day. The order of the two training methods was fully randomized. For one subject, the order may or may not change the next day. Overall, each training method had an ~50% chance to be used prior to the other across the entire study duration. The patients' parents were instructed to supervise the therapy and implemented the training order according to random order sheets assigned to their children. The compliance of both children and parents was investigated. During the 1-month follow-up, the parents and children were administered questionnaires to report compliance of the children and parents themselves. In addition, parents' and children's perception and psychological acceptance of the two training methods were also surveyed.The questionnaires are provided in the Appendix. In summary, the parents reported their children's compliance with each training method on the first day, in the first week, and the first month overall. The parents reported their compliance to their supervision duty for each training method in terms of completion of training and regularity of schedule. However, due to the influence of games or videos, most children are easily attracted by the EYEBITt method on the first day and the first week. Some children do not directly cooperate in the traditional patching method, and the error of compliance analysis results has a large impact. For these patients, we suggest that they can watch the same games or videos during the covering method training, and record and analyze the compliance in the first month after the stable training. Compliance was rated on a 5-point scale: strongly disagree, disagree, neutral, agree and strongly agree. Score: 1 point for strongly disagree, 2 points for disagree, 3 points for neutral, 4 points for agree, and 5 points for strongly agree.Both parents and children groups reported their psychological acceptance, as well as their perception of the helpfulness, of each training method. In addition, parents also reported their preference for the two methods. Responses were rated on a 5-point scale.t-test was used to compare compliance scores between the training methods. Finally, the Pearson product-moment correlation analysis was used to examine associations among compliance components. The Pearson correlation coefficient was used to examine associations among variables.The reliability and validity of the compliance questionnaire were examined. The validity of a tool represents its suitability for a particular study. The reliability of a tool represents its ability to provide consistent results. An independent sample Between October 1, 2018, and January 18, 2021, this study included 76  patients with an average age of 8.1 years. According to the diagnostic criteria for amblyopia provided by the Chinese Association for Pediatric Ophthalmology and Strabismus at the Chinese Ophthalmological Society, there were 58, 3, and 15 cases of anisometropic amblyopia, strabismic amblyopia, and ametropic amblyopia, respectively. And record other information of the patient .p-value of < 0.001, suggesting a correlation between variables, which supports the suitability of the scale for factor analysis and suggests that it has good validity.The Kaiser–Meyer–Olkin (KMO) values for the traditional patching method and EYEBIT method were 0.766 and 0.723, respectively, suggesting a strong partial correlation and indicating that the scale was suitable for factor analysis . BartletCronbach's alpha values for compliance components in the traditional patching and EYEBIT methods were 0.854 and 0.850, respectively, indicating satisfactory internal consistency and data accuracy .p < 0.05). The EYEBIT method was associated with better compliance than the traditional patching method . These findings suggest that the EYEBIT method is associated with better compliance than the traditional patching method.Compliance is the key factor affecting amblyopia treatment. This study aimed to compare parent and child compliance scores associated with the traditional patching and EYEBIT methods, both of which were experienced by all children in random order. The compliance assessment questionnaire was evaluated to confirm its suitability for factor analysis. Using factor analysis to test validity requires strong correlations among the questionnaire items indicated by the KMO and Bartlett spherical test values. The KMO value compares simple and partial correlation coefficients among the items, yielding values between 0 and 1. Suitability for factor analysis can be high, moderate, low, and none, corresponding to the KMO values of ≥0.9, 0.7–0.9, 0.6–0.7, and <0.6, respectively. The KMO and Bartlett spherical test values were both >0.7, suggesting a strong correlation among items. To further test questionnaire reliability, we examined the internal consistency of the results, using Cronbach's alpha, which revealed that the subjects' answers to the questionnaire items were consistent. Given good reliability and validity of the assessment method, we compared compliance and psychological acceptance of the participating children and their parents, showing differences between the methods used . Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.Concept and design: LL and GL. Acquisition and analysis or interpretation of data: TL and YX. Drafting of the manuscript: LL. Statistical analysis: LL and HX. Methodology: GL, LL, YX, and HX. Administrative and technical or material support: All authors. All authors read and approved the final manuscript.The work was supported in part by Startup Fund for scientific research, Fujian Medical University (grant number 2018QH1159) to LL and National Institutes of Health (grant number R43EY028778) to GL.Author GL: pending patent. Author GL is a co-founder of EyeNexo LLC, a startup company developing smartphone apps for vision tests. The mobile app used in this study was developed previously through a collaboration between Mass Eye and Ear and EyeNexo LLC, funded NIH grant R43EY028778. Author GL's financial interests are reviewed and managed by Mass Eye and Ear and Partners Health Care in accordance with their conflict-of-interest policies. EyeNexo currently does not have any commercial product or license related to the subject matter of this article. Author GL did not participate in data collection. 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.


This review discussed the effects of the impact of the Coronavirus Disease 2019 (COVID-19) pandemic on the psychological wellbeing of people with Parkinson's disease (PD) focusing specifically on depressive symptoms, anxiety levels, sleep, and quality of life (QoL). Together with motor symptoms, psychological symptoms are common and disabling conditions in the clinical course of PD becoming a relevant topic as a result of the lockdown measure due to alter their everyday life. We searched on PubMed online electronic databases for English articles published between January 2020 and 31 December 2021. Twenty-eight relevant studies were found and included in the review. Heterogeneous data emerged from the topics analyzed. Overall, data from depression studies showed significant depressive symptoms if the patient was analyzed longitudinally or vs. a control group consisting in healthy subjects, while these differences become minimal when the control group is a family member. Differently, in most of the studies reviewed there is no evidence of a statistically significant impact on anxiety disorders, nor on the quality of sleep. Conversely, PD patients showed a statistically significant negative impact of QoL compared with control groups or other neurological conditions. Although these findings must be interpreted carefully in the light of the studies' limitations, both in methodology and design, collectively our review showed that COVID-19 pandemic has had negative effects on the mental health of people with PD, due to disruption of healthcare services, loss of usual activities and supports and reduction in physical activity. In December 2019, the first cases of a disease called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were identified in Wuhan, in the province of Hubei, China   in patients with PD, focusing specifically on depressive symptoms, anxiety levels, sleep, and quality of life (QoL).To identify available studies, a search was carried out through the PubMed/Medline online database on articles published between January 2020 and the end of December 2021. The choice of this time interval was dictated by the World Health Organization who had declared the international SARS-CoV-2 outbreak a Public Health Emergency of International Concern on 30 January 2020.The designed search strategy resorted to the use of MeSH terms and keywords to search the database for the disease in combination with the pandemic context and NMS [disease  AND context ] AND [NMS ].Two independent reviewers and qualified researchers in clinical psychology screened records of search outputs for pertinence to the topic and English language only. A flow chart of the systematic literature search is reported in Experimental studies were included if they addressed the impact of the COVID-19 pandemic restrictions on depressive symptoms, anxiety, sleep, and QoL in patients with PD. No restrictions were applied as to sex, age and ethnicity of subjects, disease duration, and disease severity. Reviews, qualitative studies, correspondences, single case reports and studies written in languages other than English were all excluded. The articles passed a first screening phase, checking titles and abstracts, and a second screening phase, analyzing the full-text if they met the above criteria.Since some of the studies investigated several NMS at once, we extrapolated data on each one of them. The present review is structured into sub-sections dedicated to individual topics  and therefore the same study might figure in more than one sub-section. Finally, within each sub-section, we organized the results according to the experimental design of symptoms evaluation: assessment of patients before and after lockdown, comparisons between patients and control groups, and individual assessments conducted only in the PD patient group.After checking for duplications and compliance to selection criteria, 28 studies focusing on the impact of COVID-19 restrictions on depressive symptoms, anxiety levels, sleep, and QoL were included in the review process . A study by HØrmann Thomsen et al.  assessedTo assess depression symptoms, El Otmani et al.  evaluatevia telemedicine visits, and compared the data acquired during the last week of lockdown in Italy (24 April−1 May 2020) with those obtained during an evaluation conducted in February 2020, shortly before the lockdown. Results showed that patients did not exhibit depression, and no statistically significant difference between the two assessments was found. However, by analyzing individual scores, 4 out of the 5 patients who showed a clinically significant score for depression at baseline were found to still show the same score at follow-up. These data are consistent with existing studies pointing to a high incidence of affective disorders, including depression, in PD patients. No association was found between the difference from baseline to follow-up of GDS score and disease duration.Finally, Falla et al.  evaluateTo investigate the impact of the COVID-19 pandemic on depressive symptoms, Shalash et al.  administvia an online survey. According to the results, patients showed significantly higher HADS-D scores when compared to controls. Additionally, patients affected by sleep disorders were more likely to show a worsening in depression levels. Furthermore, when comparing data by gender, it emerged that more females  than males  manifested clinical levels of depression (p = 0.003).A study by Xia et al. , conductIn order to investigate the effect of increased stress levels caused by the pandemic on patients' mood, the authors of the study by Oppo et al.  administn = 20, 20%) and caregivers  who suffered from clinical depression during the COVID-19 pandemic, while PGIC results revealed that, whereas 36% of patients (n = 36) reported mild to moderate mood worsening, 56% (n = 56) reported no change, while only 8% (n = 8) reported mild to moderate improvement. Additionally, a high rate of agreement was observed between patients' accounts and caregivers' reports of symptom change.In line with these findings, Suzuki et al.  performen = 71). They assessed depressive symptoms in 38 PD patients and 31 of their relatives through the Japanese version of the 9-item Patient Health Questionnaire, sent to the subjects by email (from 22 April to 15 May 2020). The results highlighted that more patients  than controls  showed moderate to severe depressive symptoms (p = 0.002), and that more female patients  than females in the control group  had depression (p = 0.001). Additionally, duration and severity of disease did not emerge as risk factors for clinical depression, while the patients' perceived severity of motor symptoms did.Kitani-Morii et al.  invited A telephone interview was conducted on 45 patients and 43 healthy controls after the end of the lockdown in Turkey (15–20 June 2020) by Balci et al. , asking via telephone interviews during the lockdown in Italy (April–May 2020), to both patients and caregivers. Patients were evaluated at T0 (April–May 2020) and at T1 (June–August 2020), while caregivers were only evaluated at T0. Results showed that more patients (35%) than caregivers (21.7%) experienced depression, and a significantly higher mean HADS-D score was observed in patients compared to caregivers during the 2 months of lockdown in Italy (T0). Comparing the two patients' assessments, 35% of them showed depressive symptoms at T0, with a mild, medium, or severe intensity, and a similar trend was observed at T1 (34.1%), suggesting no change happened in patients' depression levels. Moreover, no statistically significant difference in depressive symptoms was observed both at T0 and T1 between patients treated with DBS, LCIG, and SMT, and no correlation was found between HADS-D score and disease duration. However, the absence of a pre-pandemic assessment of both groups and also of a post-lockdown assessment of caregivers prevents further comparisons, therefore it is impossible to establish whether the higher incidence of depressive symptoms in patients is actually related to the restrictions in place or if it is due to pathophysiologic predisposition or progression of PD.Lastly, Montanaro et al.  enrolledSong et al.  evaluaten = 108). Among the 86 (79.6%) patients who reported new or exacerbated symptoms, 54 (50%) indicated “feeling depressed” as the main trait; it was also the most reported symptom. However, the authors did not explore the possibility of a correlation between the subjective perception of depression and the stage of the disease, and with no pre-COVID-19 data it is impossible to determine whether the worsening is due to the pandemic or rather to the progression of the disease.A study by Guo et al.  investign = 19, 82.6%) with worsening symptoms reported a worsening in depression. In line with these findings, a case-control survey of COVID-19 and other clinical features in PD patients living in Tuscany was conducted by Del Prete et al.  did not notice any pandemic-related mood worsening. However, this outcome was gathered through a single question. Additionally, DASS-21 was performed on 120 non-COVID-19 patients but no specific data were available for the depression subscale.Similar findings emerged from the study of Janiri et al. , who cone et al.  on 740 sn = 90) of all patients reported a worsening of depressive symptoms. However, according to the PGI-I, worsening of the psychic state (including depression and anxiety) was among the most reported symptoms , in addition to general motor symptoms  and pain . Nevertheless, as only few patients reported a change in their depressive symptoms, the result of this scale could have been influenced more by a worsening of anxiety.Fabbri et al.  investigA study conducted in India by Saluja et al.  assessedn = 112, 56.3%), compared to those with no sleep disorders  and patients with pre-existing sleep disorders that did not exacerbate during the pandemic (p < 0.001). This study also suggests that there is indeed a relationship between depression and sleep disturbances.Kumar et al.  investign = 56, 13.4%) the majority of them  reported an increase in depression, while the others  registered only day-to-day changes.In a study conducted in Canada , and compared the mean HADS-D scores of the two subgroups. No statistically significant differences emerged and this could perhaps be due to the fact that the two groups had different sample sizes.A study by Knapik et al.  assessedIn a study by Dommershuijsen et al. , 844 PD n = 4) of them reported subjective worsening of depressive symptoms. Additionally, a statistically significant correlation was found between the worsening of depressive symptoms and the feeling of being alone/isolated (p = 0.017).Finally, Krzysztoń et al.  made an A study conducted in Italy by Falla et al.  highlighIn line with this result, another study conducted on two different PD cohorts, one Swedish and one Danish . Similarly, moderate to severe anxiety levels were more frequently observed in PD patients than in controls and caregivers. PD disease duration was also considered in this study, but no statistically significant correlation was found between this parameter and the severity of anxiety levels. The authors argue that this outcome could be due to worsening of pre-existing anxiety, uncertainty of treatment during isolation, and increased vulnerability to COVID-19 due to a chronic condition.Among the studies that produced statistically significant results, there is an online case-control survey which included the Persian version of Beck Anxiety Inventory-II (BAI-II), conducted online by Salari et al. . In thisn = 23, 60.5%) compared to controls . In addition, they found a positive correlation between anxiety and pre-lockdown off-motor severity. Instead, from the subjective report, it appeared that 20 patients (52.6%) reported anxiety/stress caused by COVID-19. Although the causes for subjective anxiety and stress cannot be disaggregated, the paper concluded that anxiety is frequently aggravated by restrictions.A study by Shalash et al. , collectHowever, it is worth noting that neither of the two aforementioned studies , PD patients  did not have a significantly higher prevalence of anxiety (p = 0.410). Moreover, patients with sleep disorders showed a higher anxiety level than those who did not experience sleep disturbances, indicating that anxiety has a powerful effect on sleep quality. Furthermore, results showed that females  reported a significantly higher incidence of anxiety levels compared to males , suggesting that female patients are more likely to experience anxiety.In a quantitative study, Xia et al.  studied n = 19, 48%) were significantly more likely to suffer from clinical anxiety than controls  results revealed that, among both patients and controls, 36.6% (n = 26) reported subjective worsening of anxiety and, surprisingly, the percentage was higher in controls  than in PD patients , but still not in the range of statistical significance (p = 0.25). Overall, results suggest that PD patients, especially those potentially suffering from pre-existing psychological issues, may be more likely to develop clinical anxiety in response to social distress; although, due to the lack of data on the patients' neuropsychiatric status prior to the COVID-19 pandemic, the study fails to demonstrate that the COVID-19 pandemic worsened the neuropsychiatric status of patients with PD.Kitani-Morii et al.  comparedn = 6) of both PD patients and caregivers, while other factors, such as disease severity, impacted negatively on patients with PD and were overall related to the worsening of their QoL. These findings may also indicate that, during the lockdown, the caregiver's daily burden intensified, and this may have contributed to the rise of anxiety levels not only in patients, but also in caregivers.In a study by Suzuki et al.  that invBalci et al.  examinedp = 0.023). Furthermore, among the patients enrolled in this study, there were subjects treated with DBS, LCIG, or SMT, so potential differences in anxiety symptoms between patients undergoing different treatment were also evaluated; a statistically significant correlation emerged between anxiety and different therapies: HADS-A scores were higher in SMT and LCIG than in DBS patients at T0, while at T1 a significance was only found for LCIG. This study highlighted how different treatments have different psychological effects. In fact, patients treated with DBS showed lower levels of anxiety than the other groups, probably due to the fact that DBS devices can be handled more independently. This study provides a snapshot of anxiety status in the middle of restrictions, however it only allows for comparison between groups at T0 and not after lockdown at T1, as caregivers were not re-assessed, nor are there any pre-pandemic measures to interpret the data collected during lockdown.Lastly, Montanaro et al.  assessedvan der Heide et al.  assessedIn a study by de Rus Jacquet et al. , based oKnapik et al.  evaluaten = 119, 60%) compared with patients who did not  or patients with pre-existing sleep disorders that did not worsen during the pandemic (p < 0.001). Anxiety is known to induce hyperarousal that is pathophysiologically associated with insomnia. However, lacking a measure of anxiety levels at baseline, the study cannot determine whether anxiety was a predisposing factor for the development of sleep issues during lockdown or, vice-versa, if sleep issues arisen during lockdown triggered the onset of anxiety.A questionnaire-based study by Kumar et al. , focusedDommershuijsen et al.  administn = 547) of a sample of 733 PD patients did not experience a subjective worsening of anxiety during lockdown. Furthermore, as mentioned in a previous sub-section , the study reported a mean DASS-21 total score that cannot be disaggregated into subscales, therefore not informative about patients' anxiety status. For this reason, it is not possible to make a comparison between the subjective experience of the patients and the results of the standardized scale, nor was a baseline value of the DASS-21 recorded to verify the presence of a change in anxiety levels.Although anxiety was not the focus of their study, Del Prete et al.  found thn = 1,568, 59.1%), 6.1% (n = 162) reported a worsening of anxiety symptoms, with anxiety being the fourth most frequently worsened symptom and the first non-motor one. Unsurprisingly, the aggravation of psychic state alteration was probably related to several self-reinforcing factors, such as the concomitant aggravation of motor symptoms, which are particularly sensitive to stress and may cause an anxiety/depression aggravation, and the diffuse interruption of physiotherapy and of any outdoor physical activities.With the purpose of evaluating changes in motor and NMS occurring after the first month of the 2020 lockdown (mild-March to mid-April 2020) as well as its psychosocial impact, Fabbri et al.  administn = 18) of the 47 PD patients who agreed to participate reported feeling anxious since the onset of the pandemic. Particularly, it was found that patients who exhibited the highest levels of anxiety were those with shorter disease duration, who were not involved in any patients' associations, and who were more frequently looking for information about potential PD/COVID-19 interactions on the Internet. Additionally, reduced social contacts and feelings of isolation had a significant impact on anxiety . These findings could be explained by a worsening of existing anxiety, insecurity associated with taking medication during isolation, and an increased perceived risk of contracting SARS-CoV-2 due to age and chronic condition.In another study . More specifically, PD patients reported a statistically significant worsening in several sleep patterns: quality, sleep duration, sleep disturbance, and daytime dysfunction (p < 0.001). No statistically significant differences emerged for sleep latency, sleep efficiency, and use of sleeping medication. Moreover, analyses showed that anxiety and exacerbation of PD symptoms were possible risk factors for developing sleep problems and, furthermore, it was observed that female compared to male patients showed significantly worse total PSQI scores (p = 0.009), worse sleep quality and duration, and more daytime sleepiness, resulting in poorer sleep. In line with the literature, the results of the study highlighted the presence of greater sleep disturbances in PD patients compared to healthy controls. The absence of clinical data on patients, such as duration of illness or severity of symptoms, does not allow for the investigation of the impact on sleep in individual patients.A study by Xia et al.  administn = 13, 33% vs. n = 7, 21%, p = 0.286) or the subjective report . However, from a qualitative observation, patients presented moderate to severe insomnia symptoms more frequently than their family members.A study by Kitani-Morii et al.  investigGuo et al.  measuredFollowing the COVID-19 outbreak, Janiri et al.  used telad hoc questionnaire by telephone to investigate new and worsening PD symptoms, including insomnia, following the beginning of the 2020 lockdown in Italy. Most patients  did not report new or worsening symptoms of insomnia as a consequence of COVID-19 restrictions.In their study, Del Prete et al.  administn = 109) of patients, out of a cohort of 2,653, mentioned a worsening of sleep disturbances.Fabbri et al.  asked paSong et al.  investigad hoc survey to 28 PD patients during or after the lockdown, in an unspecified timeframe. Patients were asked to indicate the perceived change in various motor and NMS caused by restrictions. The results showed that patients, on average, experienced a slight worsening of sleep, which was more frequent in females than males.In order to quantify the changes in sleep, Templeton et al.  administTo retrospectively investigate the effects of social restrictions on sleep, Balci et al.  studied n = 41) of patients reported mild to moderate worsening of sleep and 48% (n = 48) reported no change. The authors found agreement between the patients' and caregivers' reports of sleep changes. However, the use of the PGIC scale to assess changes in sleep quality may not be sensitive enough to detect such changes.To investigate changes in sleep in PD patients after the beginning of lockdown, Suzuki et al.  administad hoc developed and validated by nine experts, all proficient in managing patients with PD following standard procedure. They found that 295 (35.4%) patients experienced sleep disturbances and 199 (23.9%) reported new issues or a worsening of existing symptoms in all sleep parameters investigated. Among the entire cohort, the most reported symptom was insomnia , followed by restless legs syndrome , RBD , and sleep disordered breathing . Moreover, by comparing patients with and without new or worsening sleep disturbances, the authors detected that sleep problems were significantly associated with duration of home confinement >60 days, duration of PD ≥7 years, inadequate family support during lockdown, worsening of most motor and NMS, poor QoL, and not engaging in exercise or hobbies during lockdown. In addition, low physical activity and screen time >3 h/day before and during home confinement were associated with new or worsening sleep disturbances .Kumar et al.  investigTo assess sleep problems, Saluja et al.  administn = 263, 63.37%) did not notice any change in sleep, whereas 117 of them (28.19%) reported worsened sleep quality. Only a small number of patients  reported improved sleep quality during home confinement for COVID-19.de Rus Jacquet et al.  investigad hoc questionnaire in which patients were asked to indicate their degree of agreement or disagreement with the statement “I have more difficulty falling asleep.” The results showed that 54% of 100 patients reported no change in falling asleep.Finally, a study by Montanaro et al.  evaluateAmong the authors of longitudinal studies that reached statistically significant findings, Guo et al.  conducteSimilar results emerged from a study by Song et al. , in whicA discrepant result emerged from a study by HØrmann Thomsen et al. . In the via online video, during the lockdown in Italy, in spring 2020). The PDQ-39 summary index (PDQ-39-SI), filled out by 14 PD patients during the last week of the lockdown, showed no statistically significant difference compared to the pre-lockdown baseline. In addition, no statistically significant correlations were found between the difference in PDQ-39-SI score from baseline and follow-up and disease duration. The results could be explained by the fact that telemedicine evaluation appears to provide continuity of care, while also reducing the risk of infection in PD patients.Two longitudinal studies concluded for a non-impaired QoL in PD patients during the confinement. In the study performed by Falla et al. , QoL wasLikewise, in a sample of 12 PD patients no statistically significant findings on the impact of COVID-19 restrictions on QoL were found . Moreover, the latter correlated with loneliness and worse social health: patients reported a worsening in their social health and in social satisfaction and performance, while symptoms severity increased. These results confirmed that worse QoL is associated with both progression of disease symptoms and loneliness.In another study, Subramanian et al.  developeIn another observational study based on PDQ-8, Fabbri et al.  recordedSimilarly, in a study by Saluja et al.  conductead hoc questionnaires  who replied to a single-question on an ad hoc questionnaire reported that they were unsatisfied with their QoL during home confinement, especially due to worsening of both motor and NMS , and fear of contracting COVID-19 . Among patients who reported dissatisfaction with their QoL, almost half of them were patients who had reported new onset or worsening of sleep disturbances related to isolation. In line with these data, a statistically significant association between poorer QoL and the new onset or worsening of sleep disturbances was found (p < 0.001). Thus, sleep may have had an impact on the QoL of these patients.In Kumar et al. , more thThe results of another study  or in comfortable environments . Authors also found that per-day minutes of activity and the number of total activities decreased significantly (p = 0.022) due to COVID-19 restrictions, and that 82.14% (n = 23) of subjects self-reported that at least one symptom had worsened from moderate to severe. The authors argued that not being able to participate in structured in-person programs because of lockdown had a direct negative effect on patients' overall activity levels and disease progression, which in turn affected their QoL: such programs provide an opportunity to exercise and find a supportive environment that promotes social relationships, both relevant factors for wellbeing.In Templeton et al. , PD patiIn a study conducted in the Netherlands by Dommershuijsen et al. , the autn = 22, 47%), 2 , or 3  points . Patients suffering from PD for over 5 years experienced a significantly greater decrease in QoL compared to patients with a shorter history of the disease. Furthermore, a statistically significant association was found between changes in QoL and feelings of isolation (p = 0.009) and reduced social contact (p = 0.022).Lastly, Krzysztoń et al.  studied In conclusion, the studies presented in this section highlight a direct and indirect impact of lockdown for COVID-19 on the QoL of PD patients.The purpose of this paper was to perform a critical review of the literature that investigated the psychological impact of COVID-19 and restrictive measures on patients with PD. We therefore focused in particular on psychological aspects such as depression and anxiety, as well as on indirect measures such as the impact on sleep and QoL.The results on depression showed that, when comparing data collected during the pandemic and before, there was not a statistically significant impact on patients   from the Italian Ministry of Health.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.


Gastrointestinal (GI) cancers are an important component of the tumor. This study aimed to investigate the burden of six major GI cancers in China and globally from 1990 to 2019.We conducted a cross-sectional study based on the Global Burden of Disease Study (GBD) 2019. Indicators on incidence, deaths, disability-adjusted life-years (DALYs), and risk factors for esophageal, stomach, liver, pancreatic, colon and rectum, and gallbladder and biliary tract cancers were collected and analyzed for time trends. The contribution of each cancer and the proportion of cases in China among global cases were further reported.Global incidence cases, death cases, and DALYs of GI cancers showed an overall ascending trend over the past 30 years, but there was temporal and geographical variation across cancer types. By 2019, colon and rectum cancer had overtaken stomach cancer as the most burdensome GI cancer globally. However, stomach cancer narrowly continued to be the most burdensome GI in China. In addition, the proportion of incidence and death cases of stomach, pancreatic, colon and rectum, and gallbladder and biliary tract cancers among global cases had further increased. It was noteworthy that the burden of liver cancer in China has been alleviated significantly.GI cancers remain a major public health problem in China and globally. Despite the temporal and geographic diversity of different cancers, targeted primary and secondary prevention are still necessary for the future to face these unknown challenges. Gastrointestinal (GI) cancers mainly include esophageal, stomach, liver, pancreatic, colon and rectum, and gallbladder and biliary tract cancers. According to GLOBOCAN 2020, there would be an estimated 19.3 million new cancer cases and 10 million deaths worldwide in 2020, with GI cancers accounting for 26.4% of incidences and a serious 36.3% of deaths   2019 by utilizing the Global Health Data Exchange (GHDx) query tool (ts-tool) , 8. IndiThis study was based on a publicly available database and exempted by the Ethics Committee of Shanghai Tenth People's Hospital.via a linear regression equation: y = α + βx + ε (y represents ln (ASIR) and x refers to calendar year), to evaluate the trend in ASIR. The exact calculation was EAPC = 100*(exp(β)-1) , death rates, and DALY rates were used to better reflect actual incidence and mortality profiles. All rates are expressed as numbers per 100,000 population. In addition, an estimated annual percentage change (EAPC) was calculated xp(β)-1) . Both thNext, we explored risk factors for GI cancers and analyzed their evolution over the last 30 years in China and globally. The risk factors included body mass index (BMI), smoking, alcohol use, and diet.In addition, we performed clustering of 204 countries and territories by combining the EAPC for each cancer incidence and death rate. Finally, we analyzed the changes in the contribution of the six GI cancers in 1990 and 2019, as well as the changes in the proportion of incidence and death cases in China among global cases.All statistical analysis was performed with R software (version 4.0.5).3 to 534.6 × 103 with an average increase of 67.1% .Publicly available datasets were analyzed in this study. This data can be found here: The Global Burden of Disease Study (GBD) 2019 by utilizing the Global Health Data Exchange (GHDx) query tool (Written informed consent for participation was not provided by the participants' legal guardians/next of kin because this study was based on a publicly available database and exempted by the Ethics Committee of Shanghai Tenth People's Hospital.ZS and WX contributed to the conceptualization and design of the study. WY and ZH contributed to the acquisition of data. WX, TY, and JZ contributed to the analysis and interpretation of data. WX drafted the manuscript. ZS and ZM carried out the writing—review and editing. All authors have contributed to the article and agreed to submit this version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background and Objectives: Psoriasis is a chronic inflammatory disease whose impact on health is not only limited to the skin, but is also associated with multiple comorbidities. Early screening for comorbidities along with appropriate treatment plans can provide a positive prognosis for patients. This study aimed to summarize the knowledge structure in the field of psoriasis comorbidities and further explore its research hotspots and trends through bibliometrics. Materials and Methods: A search was conducted in the core collection of the Web of Science for literature on comorbidities of psoriasis from 2004 to 2022. VOSviewer and CiteSpace software were used for collaborative network analysis, co-citation analysis of references, and keyword co-occurrence analysis on these publications. Results: A total of 1803 papers written by 6741 authors from 81 countries was included. The publications have shown a progressive increase since 2004. The United States and Europe were at the forefront of this field. The most prolific institution was the University of California, and the most productive author was A. Armstrong. Research has focused on “psoriatic arthritis”, “metabolic syndrome”, “cardiovascular disease”, “psychosomatic disease”, “inflammatory bowel disease”, “prevalence”, “quality of life”, and “risk factor” in the past 18 years. Keywords such as “biologics” and “systemic inflammation”, have been widely used recently, suggesting current research hotspots and trends. Conclusions: Over the past 18 years, tremendous progress has been made in research on psoriasis comorbidity. However, collaborations among countries, institutions, and investigators are inadequate, and the study of the mechanisms of interaction between psoriasis and comorbidities and management of comorbidities is insufficient. The treatment of comorbidities with biologic agents, screening of comorbidities, and multidisciplinary co-management are predicted to be the focus of future research. Psoriasis, a chronic, inflammatory, relapsing skin disease mediated by T cells and characterized by erythematous scaling, affects more than 125 million individuals worldwide and imposes a huge burden on patients . As reseBibliometrics is the discipline of describing, evaluating, and predicting the current status and trends of a field using mathematical and applied statistical methods related to the number of publications in the literature . CompareWe conducted a literature search on the WOSCC database on 30 September 2022, and this process was completed independently by two researchers to ensure the accuracy of the results. Specific search strategy: TS = (psoriasis) AND TS = (multimorbid* OR comorbid* OR polymorbid* OR multi-morbid* OR co-morbid* OR poly-morbid*)  AND PY =In this study, CiteSpace (6.1.R3), and VOSviewer (V. 1.6.18) were used for data analysis and visualization. VOSviewer  is a visThe number of annual publications reflects the trends in the field. Between 2004 and 2022, a cumulative total of 1803 publications in the field of psoriasis comorbidities was included in the WOSCC, containing 1348 papers and 455 reviews. An overall upward trend in the number of publications was observed . AccordiData on countries and regions of publications were analyzed using VOSviewer and CiteSpace and visualized using Scimago Graphica for countries and regions with a total number of ≥20 publications A. The reData on institutions in the articles were analyzed using VOSviewer and CiteSpace, and those with ≥5 publications were visualized B. The reVOSviewer and CiteSpace were used to analyze author information in the articles and visualize the top 213 core authors with ≥5 publications C. The reReferences are the knowledge base of research, and reference co-citation analysis can reflect the knowledge structure of the field, trace the research evolution of the discipline, and indicate current research hotspots. The references of the obtained publications were visually analyzed using CiteSpace, and the key references with ≥10 citations were visualized A. The reThese references were further clustered B, and a Keywords are a distillation of the literature, and keyword analysis can show the focus of research and cutting-edge trends in the field. The keywords, such as “psoriasis”, “plaque psoriasis”, “co-morbidities”, and “comorbidities”, that affected the analysis were removed. Thereafter, CiteSpace was used to analyze the keywords for co-occurrence and visualize the keywords with ≥10 occurrences A. The toThe burst detection of the above keywords was performed using CiteSpace to capture the rapid increase of keywords over a period of time and reveal research hotspots in the field of psoriasis comorbidities. The burst keywords were presented in a chronological order C. NotablIn 1897, Professor Struss first pointed out the correlation between psoriasis and diabetes, initiating research in the field of psoriasis comorbidities . PsoriasThe number of annual publications reflects the trends in a discipline, and from this perspective, psoriasis comorbidities have developed rapidly in the last decade. Psoriasis has transformed from a cutaneous disease to a systemic disease state characterized by systemic inflammation, and an increasing number of diseases have been included in the category of psoriasis comorbidities . HoweverThe collaborative network of countries and regions, institutions, and authors provides a picture of the leading researchers in this field at different levels. The United States, Italy, and Germany are leaders in this field. Moreover, most of the highly productive institutions and authors are concentrated in these regions, suggesting more medical and research resources and a greater awareness of health management. Additionally, according to previous research, these regions have a higher prevalence of psoriasis, which explains the differences in geographical contribution to some extent . HoweverIn this study, the co-citation analysis of references provides an overview of the foundation and development of research in the field of psoriasis comorbidities . To bettThe relationship between psoriasis and metabolic disorders (#2) is complex. Several metabolic disorders can increase the risk of psoriasis and affect its treatment. For example, obesity is considered to be one of the risk factors for psoriasis, and the frequency of psoriasis and PASI scores tend to increase with increasing BMI ,23. WeigThe association between psoriasis and cardiovascular disease  has been demonstrated in several studies. Gelfand et al. identified psoriasis as an independent risk factor for myocardial infarction through a prospective cohort study that found a significantly increased risk of myocardial infarction in patients with psoriasis, especially in young patients with severe psoriasis . SubsequPatients with psoriasis often suffer from comorbid psychiatric disorders . Hedemann et al. found that patients with psoriasis were 1.5 times more likely to experience depression than patients without psoriasis. Additionally, anxiety symptoms 20–50%), schizophrenia (2.82%), and suicidal ideation (12.7%) were more prevalent in patients with psoriasis . The ass%, schizoMedicare databases (#8) are one of the important data sources for psoriasis comorbidity research and the main research vehicle for economic expenditure. For example, Feldman et al. retrospectively investigated comorbidities and healthcare expenditures among US patients with psoriasis through a large claims database, and the results showed that hypertension (34.3%), hyperlipidemia (33.5%), and cardiovascular disease (17.7%) were the most common comorbidities, with comorbidities resulting in more frequent medical visits and a higher healthcare burden among patients with psoriasis .The prevalence of psoriatic arthritis , the leading cause of teratogenicity in psoriasis, varies from 14% to 22.7% in patients with psoriasis . ComparePatients with psoriasis have been reported to suffer from a higher frequency of autoimmune diseases (#6), such as uveitis , inflammPsoriasis is usually lifelong, and elderly patients (#5) have a higher prevalence of psoriasis co-morbidities due to their specific physiopathological characteristics. The prevalence of co-morbidity in patients aged 41–60 years with psoriasis was 64.9%, and this prevalence increased to 89.8% in patients aged 61–80 years . TherefoKeyword analysis presents an overview of research and cutting-edge hotspots in the field of psoriasis comorbidities. In addition to previously recognized comorbidities, emerging comorbidities, such as osteoporosis and fractures, chronic obstructive pulmonary disease, periodontitis, atopic dermatitis, maternal adverse events, male erectile dysfunction, obstructive sleep apnea, restless legs syndrome, skin cancers, vitiligo, baldness, and COVID-19, have been shown to be associated with psoriasis ,69. NotaAtopic dermatitis was previously thought to involve a mechanism of inflammatory response centered on Th2/Th22 cells, unlike psoriasis, which is characterized by Th1/Th17-type inflammatory response . SubsequThe keyword burst predicts possible future frontier hotspots from another perspective. Psoriasis is a systemic inflammatory disease, and several studies have explored the link between psoriasis and comorbidities from different inflammatory mediators and signaling pathways. However, overall, the current research is too fragmented and not well connected. Therefore, the systemic inflammatory mechanism of psoriasis and its connection with comorbidities is yet to be elucidated; more in-depth research is needed in this field in the future. Biologics represent a landmark leap in the history of psoriasis treatment; in addition to significantly improving the skin damage of psoriasis, they have shown benefits for comorbidities in metabolic diseases, cardiovascular diseases, autoimmune diseases, and psychiatric disorders ,82. HoweThe treatment and management of psoriasis as a systemic disease is known to be important and complex. Currently, the treatment of psoriasis is not only focused on skin damage but also on the improvement of comorbidities and quality of life . AlthougThis is the first bibliometric study in the field of psoriatic comorbidities, providing a comprehensive overview of the knowledge structure, historical course, and cutting-edge trends in the field. Research on psoriasis comorbidities has received much attention from scholars and has been developing rapidly. Cardiovascular diseases, metabolic diseases, arthritis, and psychological disorders have been the main areas of focus of research to date, while other emerging comorbidities, treatment with biological agents, screening for co-morbidities, and integrated multidisciplinary management have received increasing attention and are possible trends in the future.