Stroke-associated pneumonia (SAP) is associated with a poor prognosis and a high mortality rate in stroke patients. However, the accuracy of early prediction of SAP is insufficient, and there is a lack of effective prognostic evaluation methods. Therefore, in this study, we investigated the predictive value of the Oxford Acute Severity of Illness Score (OASIS) in SAP to provide a potential reference index for the incidence and prognosis of SAP.We recruited a total of 280 patients with acute ischemic stroke who had been diagnosed and treated in the Zhumadian Central Hospital between January 2021 and January 2023. These patients were divided into an SAP group (86 cases) and a non-SAP group (194 cases) according to SAP diagnostic criteria by expert consensus on the diagnosis and treatment of SAP. We collated general and clinical data from all patients, including the survival of SAP patients during the follow-up period. Multivariate logistic regression was used to analyze the risk factors for SAP. Kaplan–Meier and multivariate COX regression analyses were used to investigate the relationship between OASIS and the prognosis of SAP, and a receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of OASIS for SAP.Ps < 0.05). Advanced age and an elevated OASIS were identified as the main risk factors for death in SAP patients . The risk of death in patients with OASIS of 31–42 points was significantly higher than that in patients with OASIS of 12–20 points . ROC curve analysis further showed that OASIS had a high predictive value for morbidity and the incidence of death in SAP patients.Our analyses identified body temperature, C-reactive protein, procalcitonin, OASIS, and a prolonged length of intensive care unit (ICU) stay as the main risk factors for SAP (all OASIS can effectively predict the onset and death of SAP patients and provides a potential reference index for early diagnosis and the prediction of prognosis in patients with SAP. Our findings should be considered in clinical practice. Stroke is a common clinical disease. The results of a survey conducted in 31 provinces in China in 2020 showed the estimated prevalence 2.6%), incidence , and mortality  of stroke in people over 40 years of age in 2020, with ischemic stroke accounting for 86.8% of the total incidence %, incide. TherefoWe recruited patients with acute ischemic stroke who had been hospitalized in the Department of Critical Care Medicine of Zhumadian Central Hospital between January 2021 and January 2023. Patients who met the following conditions were enrolled: (1) met the diagnostic criteria for acute ischemic stroke in the 2018 Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke  and had We collated a range of relevant data from each patient, including demographics , vital signs on admission , Glasgow coma scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, length of stay before ICU admission, emergency surgery before admission to the ICU, mechanical ventilation and daily urine volume on the 1st day of ICU, the length of ICU stay, complications  and the 28-day survival of SAP patients. Laboratory tests included white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT).All patients signed informed consent forms, and this study was approved by the Medical Ethics Committee of Zhumadian Center Hospital .The GCS was used to evaluate the level of consciousness of patients on the 1st day of ICU admission. The lower the score, the more serious the disturbance of consciousness. A score of 15 points indicated conscious consciousness, 13–14 points indicated a mild disturbance of consciousness, 9–12 points indicated a moderate disturbance of consciousness, 3–8 points indicated coma, and < 3 points indicated deep coma or brain death , body temperature, GCS, length of stay before ICU admission, emergency surgery prior to ICU admission, urine volume, and mechanical ventilation on the 1st day of ICU, and its scoring criteria are shown in Patients with SAP were followed-up for 28 days (the 1st day of follow-up was the day of SAP diagnosis daily). The endpoints for SAP patients included progression-free survival (PFS) and overall survival (OS). PFS was defined as the time from the beginning of SAP intervention to the observation of disease progression or death from any cause. OS was defined as the time from SAP diagnosis to the occurrence of death from any cause.t-test was used to compare the two groups. Measurement data that were not normally distributed are expressed as medians and inter-quartile ranges (IQR), and the Mann–Whitney test was used to compare the two groups. Count data are expressed as a frequency and percentage, and the chi-square (χ2) test was used to compare the two groups. Multiple logistic regression was used to analyze the influencing factors of patients with acute stroke complicated with SAP. A Kaplan–Meier survival curve was used to analyze the correlation between OASISs, PFS, and OS in SAP patients, and multiple COX regression was used to analyze the factors that influence prognosis and survival in SAP patients. Receiver operating characteristic (ROC) curve analysis was used to analyze the value of OASISs to predict the incidence and prognosis of SAP. A P-value of < 0.05 was considered to indicate statistical significance.All data were analyzed using SPSS (version 26.0) statistical software. The Shapiro–Wilk test was used to evaluate the normality of measurement data; if the data conformed to the normal distribution, then the mean ± standard deviation (SD) are given, and the independent sample P > 0.05). However, age, body temperature, the levels of CRP and PCT, and OASIS at admission were significantly higher in the SAP group when compared to the non-SAP group . Furthermore, the length of ICU stay was significantly longer in the SAP group .P < 0.001; OR = 1.081, P = 0.049; OR = 1.685, P = 0.023]; furthermore, a higher OASIS indicated a higher risk of SAP   and multiple logistic regression analysis was conducted using age, body temperature, CRP and PCT levels, OASIS, and length of ICU stay as independent variables. Sex, BMI, history of past illness, heart rate, respiratory rate, MAP, GCS, NIHSS score, emergency surgery before ICU admission, urine volume on the 1st day of ICU admission, length of stay before ICU admission, proportion of encephaledema and epilepsy, and WBC on admission were utilized as covariates. Analysis showed that the risk factors for acute stroke patients with SAP in acute stroke patients were body temperature, CRP and PCT levels, OASIS, and length of ICU stay at admission. The higher the levels of CRP and PCT, the higher the risk of SAP [odds ratio (OR) = 1.611, < 0.001) .Z = 1.558, P = 0.119). The 95% confidence interval range of the AUCs for each variable is shown in Multiple logistic regression analysis found that body temperature, CRP and PCT levels, and OASIS at admission were all risk factors for SAP in acute stroke patients. Next, we considered whether these factors could hold predictive value for SAP. ROC curve analysis showed that body temperature, and CRP and PCT levels had an average predictive value for SAP in acute stroke patients  and that there was no significant difference between the mid-OASIS and low-OASIS groups (P = 0.155) (P = 0.503) , a mid-OASIS group (21–30 points), and a low-OASIS group (12–20 points) . Kaplan–= 0.155) , thus in= 0.503) ; thus, OP = 0.041; P < 0.001); the risk of death was 2.784-fold higher in patients over 58 years of age than in patients under 58 years of age (95% CI: 1.041–7.449), 5.588-fold higher in patients in the high-OASIS group than those in the low-OASIS group (95% CI: 1.531–20.401), and 2.703-fold higher in patients in the mid-OASIS group than in the low-OASIS group (95% CI: 0.741–9.769)  . These dP < 0.001) with a sensitivity of 77.88% and a specificity of 68.29% . Considering the clinical practice, we believe that although the combination of OASIS + CRP + PCT improves the diagnostic value partly, it takes a long time and is not conducive to rapid diagnosis because it involves laboratory indicators and needs to collect CRP and PCT of patients. Therefore, OASIS can predict the risk of SAP and represents an objective and simple model that does not require biochemical parameters and is worthy of clinical promotion.Based on the risk factors of SAP, many researchers have attempted to establish SAP risk models using a range of risk factors, including the A2D2 score scale, the preventive antibacterial therapy in acute ischemic stroke score scale, and the AIS-APS scale . HoweverP < 0.001) (P < 0.05). To further verify the relationship between OASIS and OS, multiple COX regression analysis was performed by adding confounding factors, such as age and sex; results showed that age and OASIS were independent risk factors for the OS of SAP patients. The mortality risk for SAP patients older than 58 years was significantly higher than that for patients younger than 58 years . The mortality risk of SAP patients with an OASIS of 31–42 was 5.588-fold higher than those with scores of 12–20 scores (95% CI: 1.531–20.401). Patients with scores of 21–30 had a 2.703-fold higher risk than those with scores of 12–20 (95% CI: 0.741–9.769). These findings suggested that OASIS is closely related to death in SAP patients and that increasing age elevates the risk of death in SAP patients. Because the OASIS system includes age parameters, this study only considered the predictive diagnostic value of OASIS in terms of the death of SAP patients. ROC curve analysis showed that OASIS had a high predictive value  with a sensitivity of 77.88% and a specificity of 68.29%; the best cutoff value of OASIS for predicting death was 23 points. Thus, we have confirmed that OASIS can predict the prognosis death of SAP patients efficiently and also suggests that clinical attention should be given to SAP patients aged >58 years; in such patients, early intervention measures should be actively taken to reduce the incidence of a poor prognosis.Other studies have shown that SAP patients often have a worse prognosis, such as prolonged hospital stay and significantly increased hospital mortality, thus exerting a significant impact on medical resources and the economy. At present, the early prediction of SAP prognosis is of great significance for formulating early intervention measures, improving prognosis, and reducing mortality , 26. How< 0.001) . Huang e< 0.001) . HoweverHowever, our study has some limitations that need to be considered. First, the subjects in this study had ischemic stroke and had been treated in the General Intensive Care Department of Zhumadian Central Hospital; thus, our data are not fully representative of the general population. Second, the cases in this study were all patients with cerebral ischemic stroke patients; thus, we only considered a specific condition with limited applicability. Third, the sample size was insufficient, with only 86 SAP patients and 24 high-OASIS patients; this may be the reason for the high mortality rate of SAP. These deficiencies need to be addressed in future research.The analysis demonstrated that OASIS can effectively predict the onset and death of patients with SAP and provide a potential reference index for early diagnostic and prognostic predictions for patients with SAP that can readily be translated to the clinic. Our findings have great significance in the prevention of SAP in patients with ischemic stroke, thus increasing survival rates and improving prognosis.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving humans were approved by Medical Ethics Committee of Zhumadian Central Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.XW contributed to the conception or design of the work, acquisition, analysis, and interpretation of data for the work. HS guided article design, drafting, the work, and revised it critically for important intellectual content. JX and YL contributed to the case collection and experiments operation. YS and YY contributed to the manuscript final revision and supervision. All authors contributed to the article and approved the submitted version.


This study aimed to observe the effect of different finger rest positions on the muscular activity of the hand, forearm, arm, shoulder, thorax, and neck, as well as on the angular deviation from the neutral position of the neck, trunk, upper arm, and forearm on the working side during pre-clinical procedures.post-hoc tests were performed (α = 0.05).An experimental laboratory study was performed. Response variables were muscle activation of the abductor pollicis, brachioradialis, biceps brachii, deltoid, pectoralis major, and right sternocleidomastoid muscles and angular deviation from the neutral position of the neck, trunk, arm, and forearm during simulated clinical procedures. Independent variable was finger-rest position during cavity preparation . Class I cavity preparations (N = 120) were performed on artificial first molars  (N = 120). Muscular activation was assessed by surface electromyography and angular deviations using Software for Postural Assessment (SAPO) version 0.69. One-way analysis of variance and Tukey’s or Games-Howell’s p < 0.001) during work on tooth 36. Regarding the pectoralis major and right brachioradialis muscles, we observed that for both teeth 16 and 26, working with ergonomic rest showed less muscle activation. Muscle activation of the right biceps brachii was higher for work with no rest in both the upper and lower arches, differing significantly only from the usual rest in tooth 16 (p < 0.001), usual rest and ergonomic rest in teeth 26 and 46 (p < 0.001), and only ergonomic rest in tooth 36 (p = 0.044). In the right abductor pollicis muscle, work with ergonomic rest resulted in less muscle activation for cavity preparation in teeth 16, 26, and 36, which was significantly different from work with no rest . Regarding angular deviation, it was observed that for tooth 16, there was a greater angular deviation of the arm when performing cavity preparations with no finger rest. For teeth 26 and 46, the ergonomic finger rest provided lower angular deviation from the neutral position of the right arm. For tooth 36, ergonomic rest provided less angular deviation from the neutral neck position.For the sternocleidomastoid muscle, there was no statistically significant difference between the different rest positions. For the deltoid muscle, work with no finger rest resulted in greater muscle activation (In general, the use of non-active finger rest during simulated cavity preparations, regardless of the type of rest, provided less muscle activation and angular deviation from the neutral position of the body’s upper extremity when performing pre-clinical procedures. Musculoskeletal disorders are the most common and debilitating disorders associated with dental practice . They coDuring this learning stage, holding instruments incorrectly and adopting awkward postures, such as trunk and neck twisting, exaggerated neck bending, and improper distance from the operative field often occur , as wellTo minimize these factors, ergonomics is recommended to be included in dentistry courses . ErgonomFurthermore, strategies, such as the use of non-active fingers as a resting position on a hard tissue (tooth or bone) in the oral cavity during the execution of procedures help to stabilize the working hand , promoteThe only studies related to this topic have evaluated the effect of finger rest on muscle activity during periodontal scaling . To the Therefore, this study aimed to observe the effects of different finger rest positions on muscle activity and angular deviation from the neutral position of the upper extremity of the body during pre-clinical cavity preparations.This study was approved by the Research Ethics Committee of São Paulo State University (UNESP), School of Dentistry, Araraquara, Brazil (CAAE Registry No. 50703021.7.0000.5416), and written informed consent was obtained from all participants.This was an experimental laboratory study. Response/dependent variables included: (1) muscular activity of the hand, forearm, arm, shoulder, thorax, and neck on the working side, measured using surface electromyography (EMG); and (2) angular deviation from the neutral position of the neck, trunk, arm, and forearm, measured by the “Software for Postural Assessment,” while performing simulated clinical procedures (cavitary preparations). Independent variable was three different types of finger rest positions used during cavity preparation.The sampling unit in this study was the pre-clinical cavity preparation, and the minimum sample size was determined using data from a pilot study with 80% power and 5% significance level. This resulted in 10 teeth for each experimental condition. The teeth and finger rest positions were randomized so that 10 cavity preparations of each tooth were performed  with each type of finger rest position . The responses and independent variables of each tooth were considered for further analysis.To simulate the clinical environment, a dental phantom head  was attached to the dental chair, which has artificial resin teeth that are specific for pre-clinical cavity preparation. Using a #1014 diamond burr at low speed, class I cavity preparations were made for composite resin in the right upper first molar (16), left upper first molar (26), left lower first molar (36), and right lower first molar (46). As the artificial tooth was prepared, it was replaced with a new intact tooth for the next cavity preparation.Three different forms of finger rest positions were proposed during the cavity preparations: (1) no finger rest; (2) usual finger rest; and (3) ergonomic finger rest, which followed the recommendations of the Discipline of Ergonomics in Dentistry, São Paulo State University (UNESP), School of Dentistry, Araraquara. A micromotor and contra-angle were held using a tripod grasp  with the working hand.For “no finger rest” work, cavity preparations on teeth 16, 26, 36, and 46 were performed with the operator working in a 9 or 11 o’clock position, without supporting the inactive fingers (ring and minimum fingers) of the working hand in any location . For the “usual rest position” work, the operator chose the fingers and working positions that were more comfortable and safer, as shown in For the analysis of muscle activity, surface EMG was used, which analyzed muscles of the neck (right sternocleidomastoid), shoulder (right anterior deltoid), thorax , arm (right biceps), forearm , and hand (right abductor pollicis).This study followed the protocol recommendations for non-invasive surface EMG muscle assessment–SENIAM , as wellThe EMG signals were collected continuously for 120-s period, while the simulated cavity preparation was performed, stored on a computer, and then processed and analyzed . This peThe angular deviation from the neutral position was based on the RULA method , as wellThe measurement of angular deviations of the neck, trunk, arm, and forearm were performed by a properly calibrated and blinded researcher using “Software for Postural Assessment” (SAPO), version 0.69. In this software, a reference point is placed for the two lines traced. Vertical line represents the neutral position of the region to be evaluated, whereas the oblique line to the reference point follows the actual inclination adopted by the operator. The software then calculates the numerical value that represents the angle formed by these three points .ρ = 0.864 and p < 0.001 were obtained.The researcher’s calibration was conducted during a pilot study. It consisted of evaluating 10 angular deviations of each region in duplicate, with an interval of 1 week between assessments. Intra-examiner agreement was calculated using the Intraclass Correlation Coefficient (ρ), where p = 0.001–0.928 for muscular activity and p = 0.010–0.907 for angular deviation). A one-factor analysis of variance (ANOVA) was then performed, in which only the finger rest position was considered a factor. A tooth cannot be included as a second factor in the same analysis, since the positions for each tooth are different, and consequently, the muscle activity and angular deviation are not comparable (see post-hoc tests (depending on the condition of homoscedasticity and heteroscedasticity). The significance level adopted was 5%.Descriptive statistical analyses were performed using IBM SPSS Statistics version 27. Normality was verified using skewness ≤3 and kurtosis ≤7 . The homable see  and 2. Mp = 0.487), 26 (p = 0.630), 36 (p = 0.983), and 46 (p = 0.913).As shown in For the right anterior deltoid muscle, work with no finger rest resulted in greater and significantly different muscle activity when compared with work in ergonomic and usual rest positions .p = 0.027 and p < 0.001, respectively) and 26   .p < 0.001), usual and ergonomic rest positions in teeth 26 (p < 0.001) and 46 (p < 0.001), and ergonomic rest position in tooth 36 (p = 0.044)  .p = 0.029), 26 (p < 0.001), and 36 (p = 0.013)  .p < 0.001), 26 (p = 0.009), and 46 (p = 0.040). In tooth 16, a larger angular deviation from the neutral position of the right arm was observed when performing cavity preparations with no finger rest, thereby differing significantly from the cavity preparation performed with the usual and ergonomic rest positions. For teeth 26 and 46, the ergonomic rest position provided a lower angular deviation from the neutral position of the right arm, which was significantly different from the cavity preparation performed with no finger rests.A significant difference was observed  only forp = 0.043). It was observed that the angular deviation of the neutral position of this region was lower during the performance of the cavity preparations with the ergonomic rest position, thereby differing significantly from the cavity preparation performed with no finger rest  was not influenced by the support of the fingers. In contrast, work with ergonomic rest position on tooth 36 promoted less muscle activity in the shoulder region (right deltoid) when compared to work without finger rest. Because this tooth is located on the left side of the lower arch, it is further away from the right-handed operator; therefore, work with no finger rest may have required greater support from the right arm. This support process is guaranteed by shoulder abduction , a movemIn the muscles of the upper thorax , the performance on teeth 16 and 26 also showed lower activity in the ergonomic rest position. Work with an ergonomic rest position is taught and trained by students in the pre-clinical training phase on dental phantom heads. However, when they start clinical care, dental treatment is performed on real patients where an error could cause harm their oral or general health . TherefoWe observed that working with no finger rest resulted in higher activity of the arm muscle (right biceps brachii), regardless of the tooth prepared. In this situation, the forearm may not have stayed close to the body during work without support, and this less-pronated position required greater contraction of the biceps to promote hand stability, and consequently, higher muscle activity .Higher muscular activity of the right brachioradialis muscle was observed in work with no finger rest only in the teeth of the superior arch. Because this muscle is the main flexor of the elbow and its maximum activity occurs when there is a movement of total flexion of the joint , the greThe abductor pollicis muscle, which is an intrinsic muscle of the hand, allows the thumb to be placed in different positions to help hold instruments and fine control the fingers by combining the elements of abduction, flexion, and medial rotation in the joint . In thisIn the analysis of angular deviations from neutral positions, cavity preparation of teeth 16, 26, and 46 with no finger rest resulted in a higher angular deviation only in the arm. Meanwhile, work with no finger rest on tooth 36 resulted in greater angular deviation in the neck. As this tooth was in the lower arch and on the left side, it was further away from the right-handed operator, which may have required a greater head tilt for better visualization.The results obtained in this study are important for occupational health in dentistry, as they scientifically confirmed that the use of non-active fingers for stabilization during the execution of dental work resulted in less muscle stress in the upper limbs. Thus, this strategy may be adopted to prevent musculoskeletal disorders in dentistry. According to In general, the results of this study showed that if the operator does not necessarily use the ergonomic rest position, but adopts a form of rest for the fingers that is more comfortable and compatible with their needs, they will be working with less muscle activity in the region of the upper limbs, as well as less angular deviation from the neutral position. Although many students give up the ergonomic rest position when starting clinical care, its teaching and training is necessary because it allows them to develop a personalized rest position, which becomes habitual. These data provide information to professors in the field of ergonomics in dentistry to adopt the teaching of finger rest position for students during their pre-clinical phase, which will develop in their students the awareness of its importance for the maintenance of occupational health.A limitation of this study is the laboratory design and performance of the simulated and standardized procedures. This care was taken to control possible unforeseen events that could occur during the care of a real patient. Thus, future studies can be conducted in a real clinical environment based on the results obtained in a controlled environment. Despite this, considering the scarcity of studies on this topic, this study makes an important contribution to the field of education in dentistry.We believe that a strength of our study is the performance of electromyographic measurements and filming during the complete procedure instead of small collection cycles. We chose to conduct the methodology in this way because we believe that this would bring more reliable results and information to clinical reality and the environment.In general, the use of non-active finger rests during simulated cavity preparations, regardless of the type of rest position, provided less muscle activity and angular deviation from the neutral position of the upper extremity of the body during pre-clinical activities.10.7717/peerj.15663/supp-1Supplemental Information 1All electromyography and angular deviation measurements.Click here for additional data file.


The aim of this cross-sectional study was to determine the life satisfaction of older people living in a home environment and to find out what predictors influence it.The research involved 1,121 older people 60 years and above from the Moravian-Silesian region who live in a home environment. The short form of the Life Satisfaction Index for the Thirds Age (LSITA-SF12) was used to assess life satisfaction. The Geriatric depression scale (GDS-15), the Geriatric Anxiety Inventory Scale (GAI), The Sense of Coherence Scale (SOC-13), and the Rosenberg Self-Esteem Scale (RSES) were used to evaluate related factors. In addition, age, gender, marital status, education, social support, and subjective health assessment were evaluated.2 = 0.412; p<0.000]) and psychosocial factors .The overall life satisfaction score was found to be 36.34 (s = 8.66). The satisfaction of older people was classified into four grades: high satisfaction (15.2%), moderate satisfaction (60.8%), moderate dissatisfaction (23.4%), and high dissatisfaction (0.6%). The predictors of the longevity of the lives of older people were confirmed, both health factors  within the community care of the older people and university of third age is appropriate to increase the life satisfaction of the older people. An initial depression screening is also required as part of preventive medical examinations to ensure early diagnosis and treatment of depression. By 2050, it is estimated that one in four people will be over 60 years old, with the fastest relative increase in the over-80 age group . The proSeveral authors have defined life satisfaction. For example, Diener et al.  defines Contentment with life in old age is considered a success for older people and is associated with healthy ageing and full adaptation to old age . It is aFurthermore, research suggests that the satisfaction of life of older people is influenced by a number of factors that merit investigation. They are related to the level of education, finances, self-assessment of health, satisfaction with social support, and cohabitation in the common household . The infScientific research should aim to identify the key factors that influence the satisfaction of life and quality of life of older people . This caThe aim of this cross-sectional study was to identify the satisfaction of life of older people living in a community environment and to identify what predictors influence it. Based on the abovementioned research, we assumed that life satisfaction may be influenced by both health conditions  and psychosocial factors.The research involved 1,121 older people from the Moravian-Silesian Region who live in a home environment. Older people who did not agree to cooperate and lived in institutional care were not included in the investigation. The criteria for inclusion in the research sample were being aged 60 or older, being cognitively intact , having the ability to understand the Czech language. The exclusion criteria were as follows: disapproval of signing informed consent, mental problems with difficulties understanding and completing the questionnaire.Older people were approached in all districts of the Moravian-Silesian Region through more than 10 organizations , through libraries, and also through the Centre for Prevention and Promotion of Healthy Aging…. The questionnaires were distributed to older people in both printed and electronic form from September 2021 to March 2022. According to data from the Czech Statistical Office in 2021, there are approximately 236,000 persons over 65 years of age living in the Moravian-Silesian Region. Our sample represented 0.5% of these older people.To assess life satisfaction, we used the LSITA-SF12 (the Life Satisfaction Index for the Thirds Age—Short form) questionnaire, which contains 12 items with options on the 6-point Likert scale: Strongly Disagree (6), Disagree (5), Somewhat Disagree (4), Somewhat Agree (4), Agree (2), and Strongly Agree (1). For Items 2, 4, 5, and 6, the responses are reversed. The total scores for the 12 items to establish the Life Satisfaction score (from 12–72). Higher scores mean lower life satisfaction . We clasAnxiety and depression were measured in the psychological health assessment. Depression was measured using the Short Form of Geriatric Depression Scale (GDS-15) consisting of 15 questions (response: yes/no). Scores of 0–4 are considered normal; 5–8 indicate mild depression; 9–11 indicate moderate depression; and 12–15 indicate severe depression. The GDS-15demonstrated good reliability and validity . FountouAnxiety was assessed using the Geriatric Anxiety Inventory Scale (GAI), which consists of 20 “agree/disagree” items designed to assess typical common anxiety symptoms. The total score ranges from 0–20, and higher scores indicate more anxiety. A good internal consistency was found in the target group , high test-retest validity and correlation with other anxiety detection methods .The Sense of Coherence Scale (SOC-13) and the Rosenberg Self-Esteem Scale (RSES) were also evaluated. The SOC-13 scale consists of 13 items that comprise three components: SOC_C—comprehensibility (5 items), SOC_MA—manageability (4 items), and SOC_ME—meaningfulness (4 items). Respondents indicate agreement or disagreement on a seven-category semantic differential scale with two anchoring responses tailored to the content of each item. The total score can range from 13–91, and a higher score indicates a higher SOC . Data frThe RSES scale  is a 10-Quality of life (QoL) was assessed using the Older People Quality of life brief—OPQOL_brief questionnaire . The scaAge, sex, marital status, cohabitation, employment, and social support were assessed from social factors. Social support was evaluated only from the subjective point of view of the person surveyed by the question: “Do you have the impression that you have people close by who will give you help and support if you need it?” on a scale of 1  to 10 .Physical health was assessed by the number of illnesses regularly seen by the doctor and by a subjective health assessment, which was evaluated by one item: “How would you rate your health status?” with the possible answers: 1. Bad (I need assistance), 2. Rather bad , 3. Rather good  and 4. Good .The study was in accordance with the provisions of the Declaration of Helsinki and was approved by the ethics committees of the Faculty of Medicine, University of Ostrava (no. 14/2020). All subjects gave their written informed consent to inclusion before participating in the study.The SPSS statistical program, v. 24.0 was used for data analysis. Data were evaluated using descriptive statistics . Differences between groups were evaluated using the Kruskal–Wallis test and the independent Wilcoxon test. The correlation between the parameters was determined using Spearman’s correlation coefficient. Nonparametric tests were used due to abnormal data distribution . Multivariate regression analysis was performed using the enter method, employing all variables that showed significant association (p<0.05) in primary analysis. A p-value < 0.05 was considered statistically significant.The socio-demographic characteristics of the population are shown in The total life satisfaction score was 36.34 (CI = 35.83–36.85), standard deviation = 8.66, median = 36.00, min-max = 12–62, skewness = 0.144, kurtosis = -0.264, see First, we evaluated the difference in life satisfaction scores for the individual groups of older people. A correlation was found between higher life satisfaction ratings and lower rates of depression  and anxiety . A correlation was also found between higher life satisfaction ratings and better cohesion ratings for SOC , SOC_C , SOC_MA , SOC_ME , RSES self-esteem , quality of life , social support , subjective health , and lower age .Tables The aim of our research was to find out what factors influence the life satisfaction of the elderly. Based on previous research, we assumed that life satisfaction might be influenced by psychosocial factors, as well as by the assessment of mental and physical health. Life satisfaction in the elderly is an important topic because it can play a crucial role for successful ageing , 11, 12,In our research, it was confirmed that the predictor of life satisfaction is the subjective assessment of both physical and mental health, anxiety, and depression (model 1). Differences were also found when comparing between groups. Older people who had at least mild depression reported worse life satisfaction. Similarly, older people who evaluated their physical health as fair or poor reported lower life satisfaction. In previous research, the existence of chronic diseases , 35, 36,The second model tested confirmed the influence of psychosocial factors such as quality of life, self-esteem, sense of coherence, age, and social support on the evaluation of life satisfaction. Social support in our research was tested only by the subjective view of the person surveyed by one question, which represents a certain limit of research. On the other hand, it is the subjective perception of social support that can indicate satisfaction or dissatisfaction with social support, regardless of the number of people and contacts the person has.Sex, education, employment, cohabitation, and religion were also found in the difference testing. The improved life satisfaction was reported in our research by women, as well as older people who are in the labour force, live with someone in the same household, are married/divorced, are religious, and rate their self-esteem better.Social support , 18, 36,Pan et al.  comparedAge was also found to be a predictor of life satisfaction in our research. Older people under 75 years of age showed greater satisfaction. In the research of Tavares et al. , life saSome research has focused on other factors where the positive influence of hope has been demonstrated , 42, 43,salutor—i.e., a positive factor improving health despite adverse environmental influences. Zielinska-Wieczkowska et al. [In our research, we tested self-esteem and sense of coherence, which have not been tested as predictors of life satisfaction in previous research. The author who coined the term “sense of coherence” is Antonovsky , who tala et al.  state thFurther research should focus on effective preventive strategies that support mental health, including reducing symptoms of anxiety and depression and increasing the quality of life or sense of coherence of the elderly . Salvi  recommenAs part of policy measures aimed at preventing the effects of an ageing society and the related promotion of healthy ageing, it is appropriate to focus on improving mental health (reducing anxiety and depression), reducing loneliness, promoting a sense of coherence and self-esteem among the elderly. This activity can be carried out by community centres in non-profit organisations working with the elderly, or by third role universities . A government agency can help to support the funding of these activities.Educational activities, reminiscence therapy, music therapy, group cognitive behavioural therapy, art therapy, and cognitive rehabilitation should also be offered in these community centres for older people living in the community. These activation activities are now being realised, especially in institutional care for older people. Educational activities within third-age universities and other educational institutions for the elderly should focus on the prevention of the most frequently occurring diseases in old age such as cardiovascular and musculoskeletal disease. The advantage of third-age universities is that they can provide education in the field of disease prevention while increasing the social contacts of older people, their participation in society, self-esteem and the sense of coherence. Therefore, they can have a positive effect not only on physical health, but also on mental health of older people .Appropriate measures should be taken to prevent, detect early, and diagnose depression. General practitioners should play a crucial role and may also include depression screening as part of preventive screening. We recommend the use of the GDS-15 scale, which allows for rapid screening of depressive symptomatology. The GDS-15 scale has been widely used for the screening of depression and was valid for measuring mild and major depression . SubsequIn our research, predictors of the life satisfaction of older people living in a community have been confirmed, both health factors  and psychosocial factors . In implementing policy measures, these areas should be emphasized. The availability of educational and psychosocial activities in community care for older people is appropriate, as well as the motivation of older people to participate in these activities.S1 Data(SAV)Click here for additional data file.


The escalating incidence of Crohn’s disease (CD), a debilitating ailment that ravages individuals and their families, has become a formidable issue over recent decades.In this study, fecal samples from patients with CD and healthy individuals were investigated by means of viral metagenomics.The fecal virome was analyzed and some suspected disease-causing viruses were described. A polyomavirus named HuPyV with 5,120 base pairs (bp) was found in the disease group. In a preliminary analysis employing large T region-specific primers, it was found that HuPyV was present in 3.2% (1/31) of healthy samples and 43.2% (16/37) of disease samples. Additionally, two other viruses from the anellovirus and CRESS-DNA virus families were found in fecal samples from CD patients. The complete genome sequences of these two viruses were described respectively, and the phylogenetic trees have been built using the anticipated amino acid sequences of the viral proteins.Further research is required to elucidate the relationship between these viruses and the onset and development of Crohn’s disease. ConsequInflammatory bowel diseases (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC), represents a chronic and non-specific inflammatory disease of the intestine whose etiology has yet to be fully explicated. The affliction, which often rears its head during childhood, adolescence, or young adulthood, poses a common occurrence in the clinical milieu . DespitePodoviridae family exhibited a significant reduction in autoimmune disease patients’ intestines, underscoring the pivotal role of the viral dimension in shaping the trajectory of the disease. Zuo and colleagues have observed the enrichment of Caudovirales phage in the UC mucosa  patients who had received a diagnosis, alongside 9 fecal samples from healthy individuals at the Jingkou Community Hospital of Jiangsu, China, who had been excluded from the group of IBD by gastroscopy. The study specified certain criteria for sample selection, including no use of probiotics within 3 weeks, antibiotics, or antimicrobial agents, no intestinal tumors or other diseases of the digestive system, and residency in Zhenjiang, Jiangsu of China. To avoid the effects of diarrhea on enteroviruses, all disease samples were taken from patients in clinical remission. And all patients received standard treatment with infliximab every 2 months. Furthermore, all participants were required to be between the ages of 20–50 years old, and all individuals signed a written consent form prior to participation in the study. The demographic data and clinical characteristic of the patients included in this study were shown in 2.2.g for 10 min to remove the bacteria and large particular matter roughly. The resulting supernatant was filtered through a 0.45 um filter to exclude eukaryotic and bacterial cell-sized particles. The filtrate, enriched in viral particles, was treated with a mixture of DNases and RNase to digest unprotected nucleic acid  solution. After vigorous vortexing, the mixture was subjected to a high-speed centrifugation at 14,000 × eic acid . Total n2.3.de novo assembled using SOAPdenovo2 version r240, with a Kmer size of 63 and default settings. The assembled contigs and singlets were compared to an in-house viral proteome database using BLASTx, with an E-value cutoff of <10−5.The Illumina Miseq platform was used to generate paired-end reads of 250 bp, which were decoded using vendor software. In the present study, an in-house analysis pipeline running on a 32-node Linux cluster was used to treat the data. To improve data quality, clonal reads were removed and low-quality sequencing tails were trimmed using Phred, with a quality score threshold of ten. Adaptors were trimmed using the default parameters in VecScreen, which uses NCBI BLASTn with specialized parameters designed for adapter removal. The cleaned reads were then 2.4.In order to get a preliminary understanding of the prevalence of polyomavirus, anellovirus and CRESS-DNA virus in patients with Crohn’s disease, a nested PCR approach was employed. In addition to the samples used to construct the libraries, 22 additional samples collected from healthy individuals at Jingkou Community Hospital of Jiangsu were also included in the study. The criteria for sample selection were the same as previous 9 samples used for constructing libraries.To obtain the complete genome sequence of a novel anellovirus and CRESS-DNA virus, inverse PCR and Sanger sequencing were carried out. The primers used in there PCR steps were based on contigs of virus that were assembled from the sequence reads in the libraries. The specific sequences for each primer used in the PCR are shown in 2.5.The phylogenetic analyses were conducted using either the complete genome or partial gene sequences. The sequence alignment was performed by CLUSTAL W with the default settings. The phylogenetic trees were constructed using MrBayes3.2.7. The Markov chain was run for a maximum of 1 million generations, sampled every 50 generations, and the first 25% of Markov chain Monte Carlo samples were discarded as burn-in. Maximum-likelihood trees were also constructed to confirm all the Bayesian inference trees, using MEGA software version 10.1.8 .3.3.1.p = 0.91; Caudovirales, Podoviridae, Siphoviridae, Gyrovirus, Chicken anemia virus, while the control group demonstrated higher LDA scores in Virgaviridae, Bell oeoper mottle virus, closterovirodae, Crinivirus, Cucurbit chlorotic yellows virus, Tobacco mild green mosaic virus, and etc. (Microviridae (38.05%), and Siphoviridae (23.99%), followed by Podoviridae (12.00%), Virgaviridae (9.59%), Myoviridae (7.12%), Mimiviridae , Inoviridae (21.75%), Microviridae (7.60%), Myoviridae (6.01%), Podoviridae (4.19%), Mimiviridae  are small non-enveloped viruses with a circular double-stranded DNA genome . The genPolyomavirus, initially known as murine K virus, was first discovered in In this investigation, a fecal sample pool (human03) obtained from a Crohn’s disease patient was analyzed, and a human polyomavirus (HuPyV) were identified. The full-length genome of this HuPyV comprised 5,120 bp and had an overall GC content of 40.3%. Like other members of the polyomavirus family, it was found to code for five major proteins, including the large T antigen (LTAg) which was made up of 661 amino acids, the small T antigen (STAg) composed of 173 amino acids, and VP1, VP2, and VP3 with 357,345, and 226 amino acids, respectively. Furthermore, an agnoprotein was predicted to be present .PCR screening was performed on a total of 68 samples collected, including 46 samples used for library construction and an additional 22 samples collected from healthy individuals. In total, 37 disease samples and 31 control samples were taken. PCR screening was carried out on these samples, and the results reveals that 16 out of 37 (43.2%) samples in the disease group were positive, while only 1 out of 31 (3.2%) were positive in the control group. Subsequently, the amplified fragments were sequenced using the Sanger method, and the primers that were employed in the PCR reaction were designed based on the LTAg.With an aim to ascertain the genetic relationship between HuPyV and the other Polyomavirus species, a phylogram was constructed using the LTAg, including HuPyV and other representative polyomavirus species. The results revealed that the HuPyV was significantly distinguished from other polyomaviruses, and instead clustered with JCPyV and BKPyV, forming a separate cluster . Additio3.3.Alphatorquevirus genus. Betatorquevirus or Torque teno mini virus (TTMV), and Gammatorquevirus or Torque teno midi virus (TTMDV) are other viruses belonging to the Anellovirus group (Anelloviruses (AVs) are a group of circular single-stranded DNA viruses ranging from 2.1 to 3.9 kb in size. The most extensively researched member of this virus family in humans is the Torque teno virus (TTV), which was initially identified in the serum of a non-A-E hepatitis patient . It belous group . With thBioinformatic analysis was executed and it revealed large numbers of anelloviral reads from these libraries. A long contig of 2,957 bp was assembled from one of the fecal pools, human02, which exhibited similarity to ORF1 of anellovirus. Additionally, PCR screening was performed on a total of 68 samples, including the 46 samples prepared for the libraries and 22 samples from healthy individuals. The results indicated that 5 out of the 37 (13.5%) samples in the disease group and 5 out of the 31 (16.1%) samples in the healthy group were positive.In an effort to gain a deeper understanding of HuAV, inverse PCR was utilized to determine the complete genome sequence. The resulting genome sequence was found to be 3,512 bp in length, with a G + C content of 51.2%. Notably, four main open reading frames (ORFs) were identified within the genome, including the largest ORF, ORF1, which encodes 765 amino acids. Additional ORFs were found to encode 156, 102, and 63 amino acids, respectively .Alphatorquevirus, which was isolated from the serum of an acute non-A-E hepatitis patient (Genbank No.AF261761), the serum of TTV-infected infants (Genbank No. AB064604), and the serum of a healthy Taiwanese -encoding single-stranded DNA viruses (CRESS DNA viruses), encode replication initiator protein (Rep) and capsid protein (Cap). The International Committee on Taxonomy of Viruses (ICTV) has classified them into six families, including t plants , human  and The Cap protein (237aa) were identified, respectively . The resGeminiviridae, Genomoviridae, Bacilladnaviridae, Circoviridae, Smacoviridae, and Smacoviridae, as well as a few unclassified CRESS-DNA viruses. It was found that this newly identified CRESS DNA virus is clustered in a separate branch with other two other unclassified CRESS-DNA virus strains isolated from abalone and haddock tissues (GenBank No. AXH77057.1 and GenBank No. AXH77287.1), with which it shared 44.40 and 43.24% amino acid sequence identity, This information is illustrated in For a better understanding of the evolutionary relationship between HuCV and other CRESS-DNA viruses, a phylogenetic analysis was carried out with HuCV, the Rep-representative viruses of the families 4.Caudovirales was higher in the CD group. Three viruses, including a polyomavirus, an anellovirus, and a novel CRESS-DNA virus, were investigated through metagenomic analysis in patients with CD and healthy controls. The positive rates of these viruses were evaluated and compared between the disease groups and control groups. These findings may offer valuable insights into the etiology studies of Crohn’s disease. The differences in viral taxa between patients with Crohn’s disease and healthy controls may have clinical significance, which suggests that enteroviruses may play a role in the development and progression of Crohn’s disease. This has important implications for the diagnosis and treatment of the disease, as it may provide new targets for therapy. Besides, the differences in viral taxa may have diagnostic implications. In the present study, specific viral taxa are found to be more prevalent in individuals with Crohn’s disease compared to healthy controls, this could potentially be used as a diagnostic marker for the disease. This could be especially useful for individuals with atypical symptoms or who are difficult to diagnose using traditional methods. Moreover, the differences in viral taxa may have prognostic implications. Specific viral taxa may be found to be associated with more severe disease or worse outcomes, this could be used to identify individuals who are at higher risk for complications and who may require more aggressive treatment. Conversely, certain viral taxa are found to be associated with milder disease or better outcomes, this could help identify individuals who may not require as aggressive treatment. The differences in viral taxa may also have therapeutic implications, this could potentially be targeted with antiviral therapies, further research is needed to fully understand the nature of these differences and their implications for patient care.In this current investigation, the enteric virome was investigated in patients suffering from Crohn’s disease, as well as in healthy individuals. Despite observing no noteworthy differences in viral diversity between the disease group and the control group, the relative abundance of In interpreting metagenomic findings in Crohn’s disease, it is crucial to consider various factors that can potentially influence the gut microbiome, including ethnicity, sex, age of onset, lifestyle, known mutational signatures, and methodology (such as sequencing or antibody-based techniques). These factors may contribute to the observed differences in gut microbiome composition among individuals with Crohn’s disease and healthy controls. However, further research is needed to fully understand the complex interactions between these factors and the enteric virome in the context of Crohn’s disease. Polyomaviruses are non-enveloped, dsDNA viruses that are commonly found in the mammals. Two members of the family that have been confirmed to be linked to human diseases are the JC virus and the BK virus. These viruses have been known to induce tumors in animal models . In thisIn a study published in 1999, the viral copy number of JCV was found to be significantly higher in colorectal cancer tissue than in normal colon tissue . It’s noAlphatorquevirus (TTV). In addition, anelloviruses from humans, gorillas, and chimpanzees clustered closely together, suggesting that there may be similarities in anellovirus tropism between these closely related hominin hosts. The rate of positive viral results was similar between the disease and the control groups . These may indicate that the virus is widespread in humans, and not responsible for Crohn’s disease.In this study, a novel anellovirus was detected in the feces sample of a patient with CD, adding to the growing body of research on the association between anelloviruses and various human diseases. Anelloviruses are commonly present in healthy human viromes, but elevated viral loads have been observed in patients with severe idiopathic inflammatory myopathies, cancer, and lupus . A BayesNumerous metagenomic investigations have revealed that the CRESS-DNA virus boasts a substantial diversity, much of which is unclassified, uncultured , and preThis article provides insight into the mysterious world of gut virome in CD patients, employing the cutting-edge tool of metagenomic analysis. The study sheds light on the prevalence of three viruses in the gut microbiota, namely a polyomavirus, an anellovirus, and a CRESS-DNA virus. However, this is only the tip of the iceberg, as much larger sample sizes and concrete evidence of viral replication are imperative to unravel the intricate associations between these gut viruses and the enigmatic world of intestinal disease. The future of gut virome research is as tantalizing as it is unpredictable, with new discoveries and challenges lurking around every corner.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/The studies involving human participants were reviewed and approved by all individuals signed a written consent form prior to participation in the study, which was approved by the Medical Ethics Committee of the Affiliated Hospital of Jiangsu University (reference number:2020ahujs219). The patients/participants provided their written informed consent to participate in this study.WZ and XM investigated, conceived, and designed this study. YD, MW, and ZL collected the samples and data. YD performed the experiments and wrote the manuscript. MW analyzed the data. WZ and MX revised and edited the manuscript.This study was supported by the National Key Research and Development Programs of China (No. 2022YFC2603801) to and Funding for Kunlun Talented People of Qinghai Province, High-end Innovation and Entrepreneurship talents – Leading Talents (No. 202208170046), National Natural Science Foundation of China (Nos. 82072754 and 32170910), and Jiangsu Provincial Key Research and Development Program (No. BE2018689). All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


As the coronavirus disease 2019 spread globally, emerging variants such as B.1.1.529 quickly became dominant worldwide. Sustained community transmission favors the proliferation of mutated sub-lineages with pandemic potential, due to cross-national mobility flows, which are responsible for consecutive cases surge worldwide. We show that, in the early stages of an emerging variant, integrating data from national genomic surveillance and global human mobility with large-scale epidemic modeling allows to quantify its pandemic potential, providing quantifiable indicators for pro-active policy interventions. We validate our framework on worldwide spreading variants and gain insights about the pandemic potential of BA.5, BA.2.75, and other sub- and lineages. We combine the different sources of information in a simple estimate of the pandemic delay and show that only in combination, the pandemic potentials of the lineages are correctly assessed relative to each other. Compared to a country-level epidemic intelligence, our scalable integrated approach, that is pandemic intelligence, permits to enhance global preparedness to contrast the pandemic of respiratory pathogens such as SARS-CoV-2. The SARS-CoV-2 pandemic claimed during the last 2 years millions of deaths despite the mitigating effects of nonpharmaceutical interventions and model predictions that prepared decision makers. In fact, predictions became obsolete with emergent variants higher immune-escape and/or increased infectiousness. Even if their epidemic characteristics were known, their distant origin introduced additional uncertainty. We combine phylogenetic information from a small number of the first sequenced probes with epidemic- and human mobility information to provide country-specific epidemic projections and a simple estimate of the pandemic delay that allows an inter-lineage comparison. This global approach enables countries, especially those with low sequencing rate, to estimate when current mitigation measures need adaptation to stay efficient.The coronavirus disease COVID-19) outbreak, caused by the SARS-CoV-2 virus and first detected in China in early 2020, likely originated from the Huanan seafood wholesale market in Wuhan 9 outbrea, 2, 3 orIn contrast to policy during the early stages of the pandemic, when pharmaceutical interventions were not yet available, most current national efforts to control the virus rely on reactive strategies which alternate enhancement and lifting of NPIs, with the ultimate goal of prevention, or reduction, of pressure on national health systems. To achieve successful containment, such reactive strategies require high capacity for testing and sequencing to continuously monitor the potential emergence of novel viral strains of SARS-CoV-2, whose mutations might be responsible for more severe and/or more transmissible variants with pandemic potential . We defiAlthough the emergence of within-host variants with immune escape is likely to be relatively rare , sustainThis work answers these questions by three major contributions. First, we derive a protocol integrating phylogenetic, epidemiological, and behavioral analyses within a framework for data-driven and model-informed pandemic intelligence. Second, we demonstrate that with limited, early and noisy sequencing data, it is possible to quantify the pandemic potential of an emerging variant and predict the dynamics of subsequent national outbreaks with satisfactory precision. Finally, we propose a simple combination of the different sources of information to qualitatively compare the lineages according to their pandemic delay and find that only the combined measure can reproduce the observed differences.Blueprint for a pandemic intelligence framework. Reliably quantifying the pandemic potential of an emerging variant requires data, and acquiring data requires time. Between the time rn (VOC)  required disease , 18, 26, disease , and Nor disease . Early pFig. try Fig. C.In the following, we describe each step of the procedure, detailing our pandemic intelligence framework and the underlying modeling assumptions.Step 1: Reconstructing the origin of an emerging variant in space and time and its epidemic parameters. For all SARS-CoV-2 sequences belonging to the B.1.1.7 (Alpha), B.1.617.2 (Delta), B.1.1.529, BA.2, BA.5, and BA.2.75 (Omicron) lineages from GISAID . See Materials and Methods for details.m GISAID , 34, 33, history  is used t by v and an emerging one ω. We approximate the epidemic evolution byIn this way, we obtain an estimate of x at time t, where x and where rocedure .In the case of B.1.1.529, we obtain For further details, refer to Materials and Methods section and Step 2: Estimating the import risk of an emerging variant by country. We use monthly seat capacities of flights between airports from the Official Airline Guide . For Beures see . We exteures see .Step 3: Modeling country-level epidemic spread of an emerging variant under distinct scenarios. We use results from the previous step of the pipeline as inputs for an epidemic model in order to forecast the potential surge in cases due to an emerging variant in a target country. First, we estimate the daily number of infected people (seeds) traveling to the target country from the country where the VoC emerged (source country), based upon four elements: (i) results of our phylogenetic analysis, which inform both the growth rate and the time of emergence of the variant of concern, (ii) genomic surveillance in the source country, (iii) estimates of prevalence in the source country (incoporating under-reporting), and (iv) the import risk score of the target based on estimates from our analysis. Then, we produce short-term estimates of the daily incidence of the VoC in the target country by means of a Renewal process  between prediction scenarios and observations. The nRMSE is zero, if the observation lies in between the simulation scenarios. Otherwise, the nRMSE is the RMSE between observation and the closest prediction scenario, normalized to the range that is spanned by the observations in the respective target country . Fig. Alternative Step 3 and 4: The pandemic delay as a simple integrative measure for variant classification. Despite the simplicity of the projection approach, the numerical simulation on country level makes it difficult to summarize an emergent variant’s pandemic potential in simple terms. To close this gap, we introduce the pandemic delay y of all sequenced probes in the target country m:R as the phylogenetic estimate of the reproduction number, that is we assume that the population behaviorally and/or medically adapted to the pre-existing strains resulting in a R  because of the particularly high outflux per capita of its outbreak country (Great Britain). Again, it illustrates that the combination of all information is necessary to gain a realistic estimate of an emergent lineage’s pandemic potential.The phylogenetic information is encoded in the fitness advantage t^y r≈0.8, p≪0.001We presented an integrated framework that combines phylogenetic analysis of genomic surveillance data with international human mobility data and large-scale epidemic modeling, in order to characterize in nearly real time the pandemic potential of an emerging variant. This concept is intended to provide quantitative indicators about the ability of a variant to escape population immunity acquired by previous infections and/or vaccination, and quickly spread at a global level through human activities.Our framework naturally deals with missing and noisy information to infer, through a Bayesian approach, the most likely origin—in space (on the country level) and time—of an emerging variant and its growth rate. Spatial and temporal coordinates are used to feed an analytical technique to estimate the probability that a given number of infectious individuals, departing from the country where the variant first appeared, travel to other countries with no exposure to it. This crucial step is based on international travel data, providing information about human movements between countries. Note that our approach is more powerful than naive estimates based only on origin–destination pairs: in fact, we make full use of the knowledge we have about the underlying international travel network and its latent geometry , 45, 44,Only the early phase of spread of a new lineage is estimated and the proposed model can safely take advantages of assumptions like a homogeneous mixing and the lack of feedback loops in the epidemic dynamics.We have validated our integrated framework on existing variants, including B.1.1.7 (Alpha), B.1.617.2 (Delta), B.1.1.529 (BA.1), BA.2, BA.2.75, and BA.5 (Omicron), finding excellent agreement with independent estimates of the relevant phylogenetic and epidemiological parameters. By accounting for different scenarios in the progress of the epidemic in each country, we provide quantifiable indicators to inform decision makers and support pro-active policy interventions to mitigate the potentially harmful effect of an emerging variant, as preventing a sudden overburden of the national health care system. For the variant of most concern at the time of writing this manuscript (early 2023), BA.5, we estimate that its most recent common ancestor existed in early January 2022 , with a daily growth rate of 0.110 (95% HPD: 0.051–0.177).Overall, our findings show that it is possible to aim at pandemic intelligence, even with partial and noisy data. We must caution that the estimates of the pandemic potential of an emerging SARS-CoV-2 variant are largely driven by the uncertainty in the spatio-temporal coordinates of its origin. The Delta lineage is our most unreliable estimate Figs. –5, possiOur framework relies on the country of origin’s capacity to sequence a fraction of its positive tests for the phylogenetic analysis. Thus, it is crucial to support international efforts that enhance the diagnostic capabilities of countries , 47. HowFailures in international cooperation with a view to finding global solutions have undoubtedly shaped the COVID-19 pandemic. We have provided robust evidence that epidemic intelligence at country level could be not enough, alone, to contrast the pandemic of respiratory pathogens such as SARS-CoV-2, in the absence of well-coordinated genomic surveillance—especially in low- and middle-income countries currently lacking an adequate response capacity —and globCoVariants.org project (Our World in Data (The authors acknowledge the GISAID initiative and all the authors from the originating laboratories where genetic sequence data were generated for sharing such data through GISAID , which h project  and Our  in Data . The autpgad192_Supplementary_DataClick here for additional data file.


Background Genetic variants play a pathophysiological role in headaches, especially in migraine. The Mennonite group (MG) has been geographically and genetically isolated throughout its history, harboring a distinctive distribution of diseases.Objective To determine the characteristics of headaches in a group with direct Mennonite ancestry contrasting with other urban community members (control group [CG]).Methods Subjects with headaches were asked to complete a questionnaire covering: the type of headache, presence of aura, frequency and duration of attacks, pain location and severity, analgesic consumption, premonitory and postdromic manifestations, Depressive Thoughts Scale, Epworth Sleepiness Scale (ESS), General Anxiety Disorder-7, Patient Health Questionnaire-9 (PHQ-9), Migraine Disability Assessment, and Composite Autonomic System Score.Results We included 103 participants . Migraine was the most common headache , followed by tension-type headache . Aura was identified by 44.4% and 39.7% in the CG and MG, respectively (p = 0.689). The groups differed only concerning the frequency of retro-orbital pain , PHQ-9  and ESS  scores.Conclusion There were no major differences in the prevalence and clinical characterization of headaches between the MG and the CG. However, the latter showed more diffuse pain, sleepiness, and depressive symptoms. Specific genetic or epigenetic variants in Mennonite descendants might account for these differences. Advocating for a more radical reformation, including pacifism and the doctrine of adult baptism, the followers of the former priest Menno Simons were religiously and politically persecuted and thus ended up becoming an isolated population.The Mennonites are an Anabaptist group of Frisian/Flemish origin that originated after the Protestant Reform in the 16There are several different subgroups of Mennonites. The genetic epidemiology of complex and rare diseases and phenotypes have been described more extensively in the Amish and somewhat also in Canadian and Kansas Mennonites.About three billion people have tension-type headache (TTH) or migraine , the most common headaches in the general population.Headaches are a public health concern. Tension-type headache caused 7.2 million YLDs (years of life lived with disability) and migraine 45.1 million YLDs.The exact molecular mechanisms responsible for migraine are still unclear. It has been suggested a role for neuropeptides such as calcitonin gene-related peptide (CGRP)The phenotype of migraine might depend on genetic polymorphisms and epigenetic gene regulation. Migraine with aura (MA) and MO are associated with genetic variants that increase their risk.CALCA) expression can be modified in several ways , and the CGRP might, in turn, trigger regulatory mechanisms in neuronal and glial cells.Epigenetic processes could mediate our response to food, environment, and stress challenges, among other elements clinically known as trigger factors for migraine attacks. The CGRP gene .The present study was carried out within the genetic-epidemiological Mennogen project with the South-Brazilian Mennonite population.We evaluated the following data:epidemiological information;headache characteristics;Depressive Thoughts ScaleEpworth Sleepiness ScaleGeneral Anxiety Disorder-7Patient Health Questionnaire-9Migraine Disability AssessmentComposite Autonomic Symptom Scorerdedition (ICHD-3) criteria for migraine, TTH, and cluster headache:A filter question asked whether the participant had a headache in the past 12 months. Subjects who answered affirmatively were asked to complete subsequent questions that addressed the International Classification of Headache Disorders – 3the number of attacks ;duration ;location ;quality (pulsating or pressing);intensity ;aggravation by routine physical activity;presence of nausea, vomiting, photophobia, and phonophobia;presence of aura and its characteristics;presence of autonomic symptoms and restlessness.Premonitory and postdromic symptoms were surveyed by asking participants to select from a list in random order, those that occurred up to 48 hours before and after the headache phase, respectively. Possible answers for the premonitory phase were: phonophobia, lack of concentration, photophobia, neck pain, personality changes, mood changes, smell aversion, numbness, loss of appetite, fatigue, binge eating, unilateral rhinorrhea, unilateral lacrimation, or no symptom at all. Any additional symptoms could be reported in a text box. We analyzed the frequency of the six most common symptoms. The questionnaire was structured by a neurologist with training and experience in treating patients with headaches (EJP).Study participants were divided into two groups: Mennonite Group (MG) and Control Group (CG). Subjects were included in the MG if they had direct Mennonite ancestry, either unilateral (only father or only mother) or bilateral (father and mother). Control group members could not have any Mennonite ancestry but should be a part of the Mennonite community, sharing daily customs and habits – most cases were spouses (husbands or wives of Mennonites).All participants were older than 18 years old and suffered from headaches as defined by the ICHD-3.A pilot test involved 38 community members, ensuring the effectiveness of the methodology, correcting doubts, and adding new information to the questionnaire. The final sample was composed of individuals from the urban Mennonite communities established in Curitiba: Primeira Igreja Irmãos Menonitas do Boqueirão, Igreja Irmãos Menonitas de São José dos Pinhais, Igreja Nova Aliança, and Igreja Irmãos Menonitas do Xaxim. Other groups were invited but did not participate in the study. The lack of adherence from other centers may have been related to the difficulty in making personal contact with them, which were far from the research location of the investigators.The groups were compared concerning age, gender, type of headache, presence of aura, frequency of attacks, pain location and severity , attack duration, analgesic consumption, and characteristics of the premonitory and postdromic phases. When one of the diagnostic criteria for migraine was not met, we considered the case as probable migraine.t-test for independent samples or the nonparametric Mann-Whitney test. Regarding categorical variables, comparisons were made using the Fisher exact test or the chi-squared test. P-values < 0.05 indicated statistical significance. Data were analyzed with the computer software IBM SPSS Statistics for Windows, v.28.0 .The results were summarized using the mean, standard deviation (SD), median, minimum, maximum, and frequency. Quantitative variables were compared using the studentn = 45; MG,n = 58) whose general characteristics are summarized inthdecade of life. Most members were female, accounting for 73.3% of the CG and for 60.3% of the MG.One-hundred and twenty individuals answered the questionnaire (54 from the CG and 66 from the MG). Of these, 17 returned incomplete forms and were excluded. Thus, the final analysis included 103 subjects , exceeding the prevalence of TTH . However, the distribution of the headache types did not differ between groups.Most participants complained of moderate to severe pain occurring on 1 to 3 days per month. Chronic headache (> 14 days/month) was found in 7.5% of the CG and in 3.8% of the MG. The distribution of the severity and frequency of headaches did not show statistically significant differences between the two groups.n = 36) and 81.0% (n = 47) of the CG and MG, respectively (p = 1.00). The postdromic phase was recognized by 28.9% (n = 13) and 36.2% (n = 21), respectively (p = 0.528). However, the comparison by phase and symptoms did not differ between the two groups . The comparison between groups showed no other statistically significant difference concerning the location and laterality of pain (p = 0.055).Regarding pain location, the CG was characterized by a higher frequency of retro-orbital pain (55.6%) than that found in the MG . The duration of pain did not differ between groups  was uncertain due to the use of analgesics in all episodes. Among the rest who knew how long their attacks lasted (63.1%), about half of them reported pain that persisted for < 4 hours . Nevertheless, simple analgesics were the most widely used class of drugs , depressive thinking distortions (EPD), disability due to headache (MIDAS), and intensity of dysautonomic symptoms (COMPASS 31) between the two groups . The CGThe semiological aspects of individuals with headaches were similar between the two groups. Migraine accounted for a higher proportion of headache cases than expected in the general population. This finding is possibly due to the selection bias of the study respondents and the more significant disability caused by migraine. Still, the two groups showed a similar prevalence of MO, MA, and TTH, demonstrating that the Mennonite ancestry likely confers neither protective nor risk effects for these conditions, at least in the urban environment of Curitiba . These results shall still be appreciated with caution, considering the small sample size.The primary aura subtype is characterized by visual symptoms lasting from 5 to 60 minutes and sometimes up to 24 hours (extended aura). We found a high prevalence of MA in both groups, possibly because of methodological selection bias.A key feature of the present study was the evaluation of the clinical characteristics of migraine in two populations of different ancestries under the influence of a shared urban environment. This design allows us to distinguish the genetic contribution to the manifestation of the disorder. For this purpose, all migraine stages  were carefully evaluated. The premonitory phase is associated with hypothalamic activation,The attack pattern  was similar in both groups. In Brazil, it is estimated that 9.6% of those with headaches have more than 14 days of pain per month, while the remaining 90.4% have an episodic course.Migraine headache is usually felt over the frontotemporal region.The postdromic phase of migraine is of extreme interest, as data in the literature is scarce. We evaluated and observed that they occur and are equally prevalent in both populations, affecting about one-third of their members. Manifestations of fatigue and demotivation were the most prevalent, demonstrating that the impact of this disease goes beyond pain symptoms.The analysis of comorbidities demonstrated that the CG had more sleepiness and depressive symptoms than the MG. These variables were not sufficiently capable of influencing the migraine behavior in these groups. Regarding drowsiness, assessed using the ESS, it can occur as a prodrome, a manifestation in the interictal period, or a symptom of recovery.A strong correlation exists between migraine and depression, especially in high-frequency and chronic headaches. Buse et al.To the best of our knowledge, this is the first study to investigate headaches in the Mennonite population. However, its results must be interpreted with caution because of several limitations mainly related to the research design. The Mennonite population is relatively isolated, making it challenging to approach a large number of participants. Boldt et al.A selection method other than spontaneous participation, also including rural communities, is required to obtain more reliable results regarding prevalence. Gathering information about the familial pattern of MO and MA associated with genome sequencing would shed more light on the role of genetic variants in this population. Prospective studies using headache diaries and including a larger contingent of individuals would allow a better estimation of the migraine behavior in the Mennonite population. Currently, headache data are being collected on a larger group in a rural setting.Headaches are a very prevalent group of diseases and, especially migraine, are under genetic influence. The Mennonite population has been in a context of reproductive isolation throughout its history, resulting in its distinctive epidemiology. Our results did not show major differences in the prevalence and clinical characterization of headaches between Mennonites and non-Mennonite Brazilians in the urban environment. However, the latter showed more diffuse pain, sleepiness, and depressive symptoms.


Epidemiological evidence suggests an association between lifestyle habits  and gastric cancer (GC). However, the causal relationship remains uncertain. Therefore, the purpose of this study was to ascertain whether there is a causal connection between them.Two-sample Mendelian randomization (MR) analysis was performed using the publicly available Genome Wide Association Study summary datasets using six methods: inverse variance weighting (IVW), weighted median, MR using a Robust Adjusted Profile Score (MR.Raps), MR using a Robust Adjusted Profile Score (MR-PRESSO), Radial regression of MR, and Causal Analysis Using Summary Effect Estimates (CAUSE). A sensitivity analysis was conducted to assess the robustness of the results.In an East Asian population, we found that increased tea intake reduced the risk of GC  while there was a positive association between smoking and GC . No causal relationship between alcohol and coffee intake and GC. Sensitivity analyses demonstrated the robustness of these causal associations.Our study suggests that tea intake may reduce the risk of GC, for which smoking is a potential risk factor. Nevertheless, a larger and more diverse sample size is needed for further validation. According to the International Agency for Research on Cancer’s (IARC) 2020 findings, gastric cancer (GC), a highly aggressive and lethal malignancy, is the fourth most prevalent cause of cancer mortality globally and the fifth most common cancer overall –3. AccorCurrently, various factors have been reported that may correlate with the development of GC. In addition to inflammation , infectiMendel’s second law states that genotypes are fixed before illness onset and alleles are randomly assigned to progeny gametes at the time of gamete production. In addition, as a result of genetic variation being used as an exposure tool , Mendelian randomization (MR) studies can improve causal inference by reducing residual confounding and reverse causality –19. Herehttps://gwas.mrcieu.ac.uk/). We conducted two-sample bivariate MR analyses to assess the causal effects of lifestyle factors  and GC.We downloaded publicly available abstract-level genome-wide association study (GWAS) datasets from the MRC Integrative Epidemiology Unit (IEU) at the University of Bristol  from European and East Asian populations as exposures to analyze their correlation with GC in East Asian populations, and thus distinguish whether this correlation is biased by population stratification. The genome-wide Association Study (GWAS) pooled statistics for GC included 34,652 subjects of East Asian descent  . Table When evaluating the causal connection between an exposure and an outcome in MR, genetic variant(s) are employed as IVs. The fundamental conditions for a genetic variant to satisfy an IV are summarized as follows: (1) the variation and exposure are connected; (2) the variation has no connection to any confounding factor in the exposure-outcome relationship; (3) with the possible exception of its relationship to the exposure, the variation has no effect on the result.P < 5 × 10-5) that are strongly related with exposure were selected as IVs. We only used independent SNPs with r2 < 0.01 within a distance of 5,000 kb in order to remove the chain disequilibrium (LD) bias (2 < 0.01) were set for aggregating the data and clipping possible LD genetic variation. Furthermore, we used the PhenoSCanner database, which includes a wealth of information on SNPs that may be associated with disease and phenotype  (LD) bias . Therefohenotype , to exclhenotype . In ordeotype (2 . IVs thaInverse variance weighted (IVW) analysis was employed as the primary approach after choosing the suitable SNPs for exposures, and we augmented this with the use of numerous MR techniques based on various IVs assumptions, including weighted median (WM) , MR usinTo improve the accuracy of causal effects, we additionally calculated Cochran’s Q statistic to quantify heterogeneity across causal estimates of all SNPs in the IVW technique. In order to evaluate the horizontal pleiotropy impact of IVs, MR-Egger regression was performed. MR-Egger can use the intercept term to evaluate pleiotropy. When the intercept term is equal to zero, the results of MR-Egger are consistent with IVW, proving the absence of horizontal pleiotropy . For selMR analysis stastistics were performed using the following R version 4.2.0 packages: “TwoSampleMR” , 35, “MRwww.phenoscanner.medschl.cam.ac.uk), and did not find any such associations. Thereafter, 135, 66, 50, and 56 SNPs from East Asian populations and 86, 179, 119, and 151 SNPs from European populations were included as IVs for smoking, alcohol intake, coffee intake, and tea intake, respectively. The F-statistic indicated no bias due to weak instrumentation , coffee intake  and tea intake  and GC. There was no evidence of substantial heterogeneity (QP > 0.05 in Cochran’s Q test and Pintercept> 0.05 in MR-Egger) or horizontal pleiotropy  in these causal estimates when sensitivity analyses were performed (As shown in P = 0.032) and a negative association between tea intake and GC    Figure 2Our study examined the causal relationship between lifestyle factors  and GC lesions using a two-sample MR approach. We come to the conclusion that in an East Asian community, tea consumption is adversely linked with GC whereas smoking is favorably associated with increasing incidence of GC. We also found no causal relationship between alcohol and coffee intake with GC. Also, certain lifestyle choices  as exposure in the European population and outcome analysis in the East Asian population did not reveal a causal relationship. Our findings were valid and stable in IVW analyses before and after excluding outlier SNPs and were also stable in sensitivity analyses.Helicobacter pylori (H. pylori) is a significant risk factor for GC and its complete eradication has been shown to slow the occurrence of GC  . Moy et ce of GC , while Pdication . What’s dication  and levedication  gastric dication . Stomachdication .Our findings regarding the negative association between tea intake and GC are consistent with most, but not all, previous studies. The inverse association between tea consumption and GC can be explained by a number of biological processes. In previous studies, polyphenols in tea have been hypothesized to prevent cancer by regulating DNA methylation, histone modifications, and epigenetic abnormalities in microRNA . StudiesOur results for alcohol intake and coffee intake did not indicate a causal relationship with GC, possibly due to the following reasons: GC in cardia and non-cardia sites may have different etiologies. As for the anatomic site of gastric cancer, previous studies have evaluated the association between alcohol intake and site-specific risk, but the results have been inconsistent , 54. FurThe greatest strength of this study is the two-sample MR study design. As a result, MR analyses is an excellent method for understanding whether exposure factors contribute to a disease’s development. Moreover, we investigated the possibility of pleiotropy by using the most recent methodological developments. Based on the results of different sensitivity analyses, little evidence of pleiotropy can be found. As a result, our causal estimates are reliable and robust.It is important to note, however, that our MR analyses do have some limitations. Firstly, due to the limited information available in the IEU GWAS database, it was not possible to assess the effect of type of tea. Secondly, the identification and evaluation of abnormal genetic variants involves multiple methods, however mediators or pleiotropy cannot be completely excluded as possible influences. Thirdly, the intensity of IV depends on the sample size of the GWAS, and a larger GWAS is needed to identify more genetic variation in MR. Finally, our results are instructive for disease prevention, but further validation and analysis are still needed due to the limitations of the selected GAWS data.In summary, the results of the MR analysis suggest a causal relationship between smoking and tea intake with GC in the East Asian population. This result has some implications for the prevention and diagnosis of GC. However, due to the limitations of the study, this hypothesis needs to be supported by more high-quality cohort studies or randomized controlled trials with a larger and more diverse samples population.The original contributions presented in the study are included in the article/WH designed this study protocol and supervised the study. YG and ZW drafted the manuscript. KL performed the data analysis. YQ polished the manuscript. All authors contributed to the article and approved the submitted version.