The results showed that the factors affecting subjective sleep quality included disaster type, time elapsed after disaster, subjective health status, depression, and posttraumatic stress disorder. The factors affecting sleep medication use included age, time elapsed after disaster, and posttraumatic stress disorder. Therefore, interventions and support systems should be provided to prevent the prolongation of sleep problems.This study aimed to assess sleep problems and their underlying factors in victims of disasters such as typhoons, heavy rains, fires, and earthquakes. Data from the long-term survey on life changes among disaster victims in 2019 obtained by the National Disaster Management Research Institute were used. The study included 1358 victims of natural and social disasters in Korea between 2012 and 2018. Sleep problems were assessed using a survey on subjective sleep quality and the use of sleeping medication. The data were analyzed using the chi-square test,  The incidence and severity of major disasters such as earthquakes, floods, and tsunamis have increased worldwide, threatening the health and well-being of individuals, families, and communities ,2. DisasProblems with the quality of sleep are among the key characteristics of PTSD . Unlike Sleep disturbance observed after a disaster is related to several demographic and environmental factors . In prevAs disaster mental health is heavily affected by socio-cultural influences , survivoTherefore, this study assessed sleep problems and related factors among disaster victims to provide primary data for intervention programs that can help the victims in disaster response and recovery processes in the future.This is a cross-sectional research study designed to identify factors that affect sleep problems in adult disaster victims in South Korea.In this study, data from the 4th long-term survey on the change of life of disaster victims in 2019 by the National Disaster Management Research Institute (NDMI) were used . The surGeneral characteristics such as gender, age, marital status, education level, household type, average monthly income, smoking, and alcohol abuse were assessed. Marital status was divided into married and unmarried/divorced/separated. Education level was classified as middle school graduate or lower and high school graduate and above, and the household type was divided into single-person and multi-person households. Using the average monthly total income of all family members living with the participant, average monthly income was categorized into less than KRW 3 million and over KRW 3 million. Smoking was assessed as yes or no, and alcohol abuse was evaluated using the alcohol use disorder identification test in Korea (AUDIT-K). The AUDIT-K consists of 10 items evaluated on a 5-point Likert scale from 0 points  to 4 points . The total score ranges from 0 to 40, and a score of 15 or higher is classified as alcohol abuse .Disaster-related characteristics included items related to disaster type, post-disaster period, and injury/illness damage. Disaster types referred to natural disasters, including typhoons, heavy rains, fires, and earthquakes. Time elapsed after a disaster was calculated as the period from the time of disaster until the 2019 survey, and was categorized as 2 years or less, 3–5 years, and 6–7 years. Injury/illness damage was assessed as yes or no using the item “Did you suffer injury or illness damage from the disaster?”Subjective health status was evaluated using a single item assessing current overall health status. The item was evaluated on a 7-point Likert scale from 1 point (“very bad”) to 4 points  and 7 points (“very good”), and the higher the score, the greater the subjective health status. A subjective health status score of 1–3, 4, and 5–7 was assessed as bad, normal, and good, respectively.Psychological factors included depression, anxiety, PTSD, and resilience. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) , which wAnxiety was measured using the Generalized Anxiety Disorder-7 (GAD-7) scale  translatSimilarly, PTSD was measured using the Korean translated version of the revised impact of event scale (IES-R) of Weiss and Marmar , and itsSocial factors included social support and social maladjustment. Social support was measured using the social support tool developed by Park  and modiSocial maladjustment was assessed using the work and social adjustment scale developed by Mundt, Marks, Shear, and Greist , which cSleep problems were assessed using items on subjective sleep quality and use of sleeping medication from the Pittsburgh Sleep Quality Index (PSQI) . SubjectUse of sleeping medication was assessed using the item “how often did you take medications ?”, which was evaluated on a 4-point Likert scale from 1 point  to 4 points (“very often (nearly every day when necessary)”). In the analysis, there were no significant differences in variables such as depression, anxiety, PTSD, social support, and social maladjustment between the group taking sleep medication 1–2 times a month, the group taking it 1–2 times a week, and the group taking it daily. As such, “not at all” was classified as “not taken,” and “sometimes (once or twice a month when necessary)”, “occasionally (once or twice a week when necessary)”, and “very often (nearly every day when necessary)” were classified as “taken”.Researchers of the NDMI visited individual households and collected data through face-to-face interviews. After the NDMI’s approval, data were obtained in an anonymous format. Analysis of the data was performed after receiving Institutional Review Board (IRB) approval (no. KNU-2021-0009).t-test. Using the SPSS IBM 25 program , binomial logistic regression was performed to analyze factors that affected sleep problems.The participants’ characteristics were analyzed using descriptive statistics, and the differences in sleep problems according to the characteristics of the participants were analyzed by the chi-square test and Among the 1358 participants, 626 (46.1%) and 732 (53.9%) were male and female, respectively, and the mean age of the participants was 49.57 ± 12.30 years. In total, 974 (71.7%), 1083 (79.7%) and 1284 (94.6%) participants were married, high school graduates, and lived in a multi-person household, respectively. Of the participants, 687 (50.6%) had an average monthly income of more than KRW 3 million, while 238 (17.5%) and 35 (2.6%) were smokers and alcohol abusers, respectively. For disaster type, 413 (30.4%), 397 (29.2%), 351 (25.8%), and 197 (14.5%) participants suffered from heavy rain, earthquake, typhoon, and fire, respectively. The time elapsed after the disaster was less than 2 years and 3–5 years for 660 (48.6%) and 529 (39.0%) participants, respectively. The majority of the participants (1282 (94.4%)) did not report injury or illness caused by the disaster, and most of them (853 (62.8%)) had a good subjective health status. The mean score for depression, anxiety, and PTSD was 2.74 ± 4.05, 2.07 ± 3.19, and 13.78 ± 14.64 points, respectively. The mean score for social support and social maladaptation was 41.46 ± 7.54 and 7.84 ± 4.22 points .Among 1358 participants, 313 (23.0%) had poor subjective sleep quality. Those with the characteristics of being female, 40–64 years old, married, an under middle-school graduate, living in a single-person household, having an average monthly income of less than KRW 3 million, being a non-smoker and a victim of heavy rain and fire, and having a disaster experience within the last 2 or 6–7 years had a lower subjective sleep quality. Additionally, the higher the severity of depression, anxiety, PTSD, or social maladjustment, and the lower the social support, the lower the subjective sleep quality. There was no significant difference according to other variables .In this study, 141 (10.4%) participants used sleep medications. Participants over the age of 40, who were married under middle-school graduates, with an average monthly income less than KRW 3 million, and had a disaster experience within the last 2 years and a low subjective health status, displayed sleep medication use. Additionally, the higher the severity of the depression, anxiety, PTSD, or social maladjustment, and the lower the social support, the higher the use of sleep medication. There was no significant difference according to the other variables .2 = 0.37 with an explanatory power of 37.0%. The classification accuracy was 83.5%, which was satisfactory. The Hosmer–Lemeshow goodness-of-fit test showed p = 0.915, suggesting that the model was statistically suitable.The gender, age, marital status, education, type of household, average monthly income and smoking status, which were general characteristic variables with significant differences in subjective sleep quality, were used as control variables. Disaster type, time elapsed after disaster, subjective health status, depression, anxiety, PTSD, social support, and social maladjustment were included as independent variables. The categorical variables were processed as dummy variables to analyze factors that affected the subjective sleep quality. Subjective sleep quality was classified as “good” (0) and “bad” (1). The regression model had Nagelkerke RThe subjective sleep quality odds ratio increased 2.75 and 1.66 times when the disaster type was a typhoon and heavy rain, respectively, compared to an earthquake, suggesting that typhoons and heavy rains led to poor subjective sleep quality compared to earthquakes. The subjective sleep quality odds ratio increased 0.31 times when the time elapsed after a disaster was 3–5 years compared to within 2 years, suggesting that the subjective sleep quality was better when the elapsed time after a disaster was 3–5 years. The subjective sleep quality odds ratio increased 1.92 and 3.49 times with a normal and low subjective health status, respectively, compared to high subjective health status, suggesting that the subjective sleep quality was worse in those with normal and low subjective health status. Additionally, every one-point increase in the PTSD scores increased the subjective sleep quality odds ratio by 1.03, suggesting that the higher the severity of PTSD, the lower the subjective sleep quality .2 = 0.21 with an explanatory power of 20.8%. The classification accuracy was 89.2%, which was satisfactory. The Hosmer–Lemeshow goodness-of-fit test showed p = 0.571, suggesting that the model was statistically suitable.Variables with significant differences in sleep medication use were included as independent variables, and categorical variables were processed as dummy variables in analyzing factors that affected sleep medication use. The age, marital status, education, type of household, and average monthly income, which were general characteristic variables related to significant differences in sleep medication use, were put into control variables. Use and no use of sleep medications were assigned 1 and 0, respectively. The regression model had Nagelkerke REvery one-year increase in age increased the odds ratio of sleep medication use by 1.03 times, suggesting that the sleep medication use increased. The sleep medication use odds ratio increased 0.49 times when the time elapsed after a disaster was 3–5 years compared to within 2 years, suggesting that sleep medication use decreased. Additionally, every one-point increase in the PTSD scores increased the sleep medication use odds ratio by 1.03, suggesting that the higher the severity of PTSD, the higher the sleep medication use .In this study, the factors that affect sleep quality and sleep medication use among victims of disasters, such as typhoons, heavy rains, fires, and earthquakes, were analyzed. The main points of discussion based on the results of this study are as follows.In our study, 23% and 10.4% of the participants showed poor subjective sleep quality and used sleep medications, respectively. As there are differences in the characteristics of the participants and methods used for assessing sleep problems, direct comparison is difficult; however, the proportion of participants with poor sleep quality is higher than the 6.9%  and 15% An analysis of subjective sleep quality according to the characteristics of the participants showed that females over the age of 40 who were married, graduated from middle school or lower, had an average monthly income of less than KRW 3 million, were non-smokers, were victims of heavy rain or fire, and had experienced a disaster within the last 2 or 6–7 years had lower subjective sleep quality. In previous studies, the demographic characteristics shown to be related to duration of sleep difficulties were being female ,37, oldeAdditionally, the higher the severity of the depression, anxiety, PTSD, or social maladjustment, and the lower the social support, the lower the subjective sleep quality. This corroborates the results of a previous study, in which negative psychosocial factors, including financial strain, social isolation, low emotional support, negative social interactions, and psychological distress, were found to be related to sleep difficulties . Social A binary logistic regression analysis showed that marital status, household type, disaster type, time elapsed after a disaster, subjective health status, depression, and PTSD affect the sleep quality of disaster victims. In a previous study, women and older people were reported to be mentally vulnerable to disaster-like situations , and OnoThe subjective sleep quality odds ratio increased by 2.75 and 1.66 times when the disaster type was typhoon and heavy rain, respectively, compared to when it was an earthquake, suggesting that typhoon and heavy rain led to poor subjective sleep quality compared to earthquakes. In Korea, heavy rains caused by typhoons are frequent, and earthquakes are relatively rare. It is thought that a more detailed analysis of the difference in sleep quality according to the disaster type should also include the scale of damage caused by the disaster and the level of recovery.We also observed that the subjective sleep quality odds ratio increased 0.31 times when the time elapsed after a disaster was 3–5 years compared to within 2 years, suggesting that the subjective sleep quality was better when the time elapsed after a disaster was 3–5 years. It is possible that the victims gradually recover from the trauma and that the quality of sleep improves simultaneously . HoweverThe subjective sleep quality odds ratio increased 1.92 and 3.49 times in normal and low subjective health statuses, respectively, compared to high subjective health status, suggesting that the subjective sleep quality was worse in those with normal and low subjective health status. The participants’ health problems were not assessed in detail in this study. However, since physical illness is highly related to sleep difficulties , it woulIn this study, we also observed that participants over the age of 40 who were married, graduated from middle school or lower, had an average monthly income of less than KRW 3 million, had experienced a disaster within the last 2 years, and had a low subjective health status used sleep medications. Additionally, the higher the severity of depression, anxiety, PTSD and social maladjustment, and the lower the social support, the higher the sleep medication use. Our analysis also shows that age, time elapsed after a disaster, and PTSD significantly affect sleep medication use. Every one-year increase in age increased the odds ratio of sleep medication use 1.03 times, suggesting that the sleep medication use increased. The quality of sleep decreases as age increases; thus, it is thought that more people would require sleep medications to manage sleep difficulties. The sleep medication use odds ratio increased 0.49 times when the time elapsed after a disaster was 3–5 years compared to within 2 years, suggesting that sleep medication use decreased. The risk of sleep medication use should decrease as the time elapsed after disaster increases. However, there are individuals who experienced a disaster 6–7 years ago and still require sleep medications, and it is worth noting that the proportion of those who need sleep medication is greater here than in those who experienced a disaster 3–5 years ago. Considering that PTSD is also a factor that affects sleep medication use, it would be important to develop proactive measures that can help disaster victims recover from PTSD quickly. Additionally, it would be necessary to manage it with continuous monitoring to prevent prolonged sleep difficulties.In a study of the victims of the 2011 Great East Japan Earthquake, financial hardship carried a high risk of lowering sleep duration and quality, and significantly increased the risk of inadequate sleep and insomnia. Furthermore, home destruction was a significant predictor of sleep medication use . As the The recommended sleep duration per day is approximately 7–8 h, and more or less sleep is related to various health problems such as high blood pressure, cardiovascular disease, diabetes, obesity ,47, and The limitations of this study are as follows. First, the subjective sleep quality of the participants was evaluated and analyzed as a binary variable. Sleep medication use was also assessed depending on the response of the participants. Therefore, further studies are required to assess objective sleep quality and verify the relationship between sleep quality and PTSD caused by disasters. Moreover, it is also necessary to conduct a study that assesses sleep medication use based on the type and dose of actual drugs rather than participants’ responses. Second, as this was a cross-sectional research study, it was not possible to verify the causal relationship of factors that affect sleep quality. A longitudinal observation of factors that affect the sleep of disaster victims and a chronological analysis of the accumulated data is required. Third, related variables, such as the victims’ sleep difficulties before the disaster, traumatic events, the scale of damage caused by the disaster, and the recovery level, were not considered in our study. It would be necessary to analyze related factors in the consideration of the effects of these variables on sleep quality and the severity of PTSD induced by disasters. Nevertheless, this study is meaningful in that it is based on panel data from disaster victims in Korea, and assessed factors that affect sleep quality and sleep medication use.It is difficult to predict the time and place of natural disasters, and anyone can be a victim of disasters. Therefore, it is necessary for everyone to be interested and actively facilitate victims’ quick recovery during disasters. Attention to disaster-related sleep quality problems is essential to alleviating PTSD among survivors. Our study observes that the risk of low sleep quality and sleep medication use is greater among the socially underprivileged who have low education levels, low incomes, high social maladjustment, and low social support. Moreover, the time elapsed after disaster and PTSD were highly related to sleep quality and sleep medication use. Therefore, more focus on preventing and mitigating sleep difficulties in the event of disaster-related damages would be important. In particular, rapid therapeutic interventions should be provided to prevent prolonged sleep difficulties following disasters, and measures for continuous interest and support systems rather than short-term support need to be developed.


Twenty patients had their appendage occluded percutaneously . The other twenty underwent thoracoscopic occlusion . Percutaneous patients were on dual antiplatelet therapy for the first three months and aspirin thereafter, whereas the others received no anticoagulant/antiplatelet therapy from the day of surgery. Follow up included TEE, CT scan, and periodical clinical evaluation. Results: Mean duration of procedures and hospital stay were comparable. All patients had complete exclusion of the appendage; at a mean follow up of 33.1 ± 14.1 months, no neurological or hemorrhagic events were reported. Conclusions: A heart team approach may improve the decision-making process for stroke and hemorrhage prevention, where LAAO is a therapeutic option. Percutaneous and thoracoscopic appendage occlusion seem to be comparably safe and effective. An epicardial LAAO could be advisable in patients for whom the risk of bleeding is estimated as being too high for post-procedural antiplatelet therapy.Background and Purpose: Left atrial appendage occlusion (LAAO) is an accepted therapeutic option for stroke prevention; however, the ideal technique and device have not yet been identified. In this study we evaluate the potential role of a heart team approach for patients contraindicated for oral anticoagulants and indicated for left atrial appendage closure, to minimize risk and optimize benefit in a patient-centered decision-making process. Methods: Forty patients were evaluated by the heart team for appendage occlusion. Variables considered were CHA The ESCThe majority of patients undergoing surgery for atrial fibrillation will have their LAA addressed. Excision with suture closure has been part of the Maze operation since the first report in 1987 . More reSeveral percutaneous devices are available for occlusion of the LAA (LAAO-P), the most frequently implanted and studied is the Watchman . Protect AF, Prevail, Ewolution trials, and others  have docHere, we present our experience and the clinical impacts of a heart team approach to patient selection for LAA exclusion, either with a standalone, totally thoracoscopic, or a percutaneous procedure. This was carried out to minimize the risk and optimize the outcome for each individual patient.Forty patients with AF and a contraindication to oral anticoagulants underwent heart team evaluation for left atrial appendage exclusion for systemic embolism and hemorrhage prevention between 2017 and 2020 .2DS2VASc > 2, HASBLED > 1. Patients were contraindicated anticoagulation for the following reasons: cerebral hemorrhage (n = 12), non-cerebral life threatening hemorrhage (n = 12), non-life-threatening repetitive bleeding (n = 10), or having an underlying condition associated with high bleeding risk . Criteria for exclusion from the study included previous PTCA (<1 year), comorbidity with life expectancy <1 year, heart disease requiring combined procedure, symptomatic carotid disease, and presence of left atrial appendage thrombus.The team met on a monthly basis and was composed of two electrophysiologists, a cardiac surgeon, an anesthesiologist, a neurologist, and a referring physician. All of the participating patients had a history of bleeding, requiring treatment/intervention and/or cardioembolic event, CHA2DS2VASc, HASBLED [The variables identified for directing patients to a surgical or percutaneous group were past medical history, underlying condition that contraindicated oral anticoagulation and necessitated its interruption, risk of bleeding recurrence, history of blood transfusion, anatomy of the appendage on CT scan, lung function, nature of the acute/recent hemorrhagic event, expected time for antiplatelet/anticoagulation reintroduction, CHA HASBLED , and pat HASBLED , and pub HASBLED ,12,13,14 HASBLED   for procedural aspects and appendage classification, in accordance with Di Biase et al.  Table 2Table 2, To allow the heart team members to be involved in both treatment options, percutaneous and thoracoscopic procedures were scheduled on the same day. Both procedures were performed under general anesthesia, and the same anesthesiology protocol  was followed. All device deployments were guided by transesophageal echo and additional fluoroscopy or direct-view in percutaneous or thoracoscopic approach respectively. Approval was sought from the appointed hospital’s ethics committee (A391-11-2020), and informed consent was obtained from the patients.Categorical variables are reported with numbers and percentages, continuous variables with mean ± SD, median and IQR (Q1–Q3). For statistical analysis the Shapiro–Wilk test was used to test the normality of the continuous variables, the Wilcoxon rank sum test was used to compare groups of nonparametric data. The comparisons between groups of categorical data were performed using a Chi square test if expected cases were at least five, or Fisher exact test if expected cases were less than five. The significance level was set at 0.05 for all analysis, and statistical analysis was performed using SAS version 9.42 insufflation and opening the pericardium, the LAA was measured with a dedicated sizing-tool and the AtriClipPro2 was positioned under direct view and TEE guidance.The procedure was performed as described previously . BrieflyUnder general anesthesia and standard monitoring, the Watchman device  was implanted at the ostium of the LAA via a transseptal puncture and through femoral access, as described .Echocardiography plays an important role when LAAO is a therapeutic option, not only during the pre-procedural phase, to detect the presence of LAA thrombus or anatomical aspects influencing percutaneous device selection , but alsIn the LAAO-P group, dual antiplatelet therapy for three months and aspirin 100 mg/day thereafter were prescribed.In the LAAO-T group heparin, anticoagulants and antiplatelet therapy were stopped on the day of the procedure and no further therapy was prescribed thereafter.All patients attended an outpatient clinic visit, including full physical examination and completion of a QVSFS questionnaire (questionnaire for verifying stroke-free status (QVSFS))  at 1, 3,For appendage closure assessment, TEE at 1 month and CT scan at 3 months were planned for leak detection and stump measurement in both groups. Criteria of success in the watchman group were absence or presence of minor and major leaks of less or more than 5 mm, respectively, in accordance with Wunderlich et al.  Figure a,b. In t2DS2VASc were higher, and history of non-cerebral non-GI bleeding was more common in the LAAO-P group; whereas, previous GI bleeding and all other variables were equally distributed among the two groups  were more common in the LAAO T group, as HASBLED and CHAo groups .Mean duration of the procedure was 54.4 ± 12.7 min in the LAAO-P and 52.2 ± 14.3 min in the LAAO-T group. Post-procedure mean ventilation time was 11.2 ± 6.4 min for LAAO-P and 15.8 ± 16.4 for LAAO-T, with mean hospital stay of 3.4 ± 0.7 in LAAO-P and 3.8 ± 0.9 days in LAAO-T. No major complications occurred in either of the two treatment groups: with one pericarditis in the LAAO-T group, and one groin hematoma in the LAAO-P group .All patients were returned to the ward after the procedure, except for one patient in the LAAO-T group, who required slow respiratory weaning, due to COPD. No procedure related pulmonary morbidity or deaths were documented perioperatively or during follow up. One patient who was eligible for both procedures was treated surgically, due to her preference. The anatomies of the appendages were comparable between the two groups . TEE andFollow up was complete for all 40 patients (mean 33.1 ± 14.1). No hospital readmission was documented for cardiovascular or neurological events, and in QVSFS consultations no suspicions of neurological events were reported.The LAA is known to be an important source of thrombi formation, leading to strokes or transient ischemic attack. Anticoagulants are highly effective, but with anti-vit K there are concerns regarding interactions, the challenges associated in maintaining therapeutic levels, and patient compliance , and theThe purpose of a heart team is to utilize multidisciplinary expertise in decision-making for the treatment of complex patients. To our knowledge, this is the first heart team guided approach for left appendage exclusion in patients contraindicated for OAC/NOAC, considering a percutaneous or thoracoscopic approach. We hypothesized that the ideal device and implantation technique for each individual patient is still lacking, and that a heart team approach in decision-making could tailor the most reasonable therapeutic option, balancing risk and benefit, for each individual patient, in an effort to optimize the outcome. All percutaneous intracardiac occlusion devices have a less invasive implant procedure but require periprocedural OAC/NOACS and a subsequent switch to antiplatelet therapy, ideally for a short period of time. Extracardiac thoracoscopic clipping of the LAA is more invasive, since it demands access to the chest, however, it does not require post-procedural anticoagulant or antiplatelet treatment ,9.2DS2VASc score (±SD) 4.1 ± 1.4, and mean HASBLED score 2.9 ± 1.0) who underwent standalone thoracoscopic stapler and loop LAA removal, all appendages were successfully amputated and no hospital or major procedure-related complications were reported. All patients received one month of anticoagulation, and antiplatelets were prescribed only in those already taking them before surgery. Follow up was completed in 198 patients (98%), and over a mean period of 48 months (range 12–110) two cardiogenic strokes were reported (0.25 event per 100 patient-years) and confirmed by MRI, concluding that their technique was safe and effective for LAA management, providing acceptable mid-term systemic embolism prevention without anticoagulation [Percutaneous closure with a Watchman device has been extensively studied in the Protect AF and Prevail trials compared to anti-vit K ,32. Onlygulation .In this study, the therapy was chosen according to each patient’s expected outcome and the risk, safety, and efficacy of two standard procedures: standalone totally thoracoscopic LAA exclusion with clipping, or percutaneous closure with a Watchman.The main variables we found to be essential for selection were the HASBLED score, previous chest surgery, CT scan report, and comorbidities with a known risk of bleeding, documented or not in the medical history . The HASBLED score is a scoring system for bleeding, but over a value of 5, no bleeding risk data are available . A HASBLProcedural times and average length of hospital stay were almost identical in both groups, as well as the post-procedural ventilation time. Before the procedure, 42% of patients received blood transfusion and of those 76%, were enrolled in LAOO-T, since antiplatelet therapy was deemed to have a negative prognosis in the long term, this may have contributed to there being no hospital readmissions nor blood transfusions during follow up; consequently improving quality of life.The strict follow up and consultation of the regional healthcare database enabled us to document the absence of neurological/cardiological events and hospital readmissions of any cause, which is in line with previous reports ,9. ThereThis was a single-center pilot prospective study with a small sample size, and on this basis cannot provide certain conclusions. The length of follow up is a major limitation. The possibility of providing a percutaneous and a totally thoracoscopic program for appendage closure is not available in all cardiac centers for these reasons, the reproducibility of data, the interpretation, and the decision-making processes need to be confirmed in larger studies. Furthermore, the HASBLED score is a validated predictive tool for bleeding, not including disease related bleeding/re-bleeding risk on antiplatelet therapy, and, therefore, the decision-making process of the heart team was based upon variables not selected through statistical analysis and applied to individual clinical data. In conclusion, since a larger randomized controlled study is required to better understand and estimate the risk and benefits, comparing both treatments, the findings of this study should be taken as preliminary.A multidisciplinary heart team approach for patients contraindicated for oral anticoagulants and indicated for left atrial appendage closure, offering an epicardial thoracoscopic, as well as an percutaneous endocardial, treatment option, could be a safe and effective strategy for optimizing results and minimizing risks. The main variables we found to be essential for selection were the HASBLED score, CT scan report, lung function previous chest surgery, and comorbidities with known risk of bleeding documented or not in the medical history. These risk profiles and long-term benefits of a LAAO procedure should be taken into account and discussed with the patient when choosing a treatment strategy. Epicardial LAA clipping could be advised in patients in whom the risk of bleeding is estimated as being too high for antiplatelet therapy.


To compare the effects of self-selected and predetermined intensity on sleep quality and duration, daytime sleepiness, and sleep efficiency of adolescents with obesity after 12 weeks of aerobic training.Thirty-seven adolescents (12 girls), 13-18 years old, with obesity (BMI = 95th) were randomized into a predetermined intensity group (PIG), exercise intensity around 60-70% of heart rate reserve; or self-selected intensity group (SIG), the adolescents chose the speed/intensity at the beginning of each session and were able to change it every 5 minutes. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to assess sleep outcomes.No differences were observed for PSQI , sleep duration , ESS , and sleep efficiency  for the PIG and SIG groups, respectively.Aerobic training at a self- selected or predetermined intensity does not modulate sleep quality, sleep duration and efficiency, and daytime sleepiness, independent of intensity. The epidemic of obesity in children has occurred in parallel with a reduction in sleep duration 4. Studies show an association between sleep and obesity6, leading to a risk of weight gain and obesity during adolescence7. Alterations in sleep quantity, quality, daytime sleepiness, and fatigue could be associated with reduced physical activity levels in adolescents with obesity8.The high prevalence of childhood obesity is one of the major public health problems worldwide10. Regarding individuals with obesity, the majority of the research has been conducted in adults12, and data on the pediatric population are scarce. Mendelson et al., (2016) examined the impact of exercise training  in a sample of adolescent  and 20 healthy-weight, on sleep duration, sleep quality, and physical activity. The authors reported increased sleep duration and sleep efficiency in adolescents with obesity.Although small, the effects of aerobic training on sleep parameters are reported as beneficial, in particular, sleep quantity and quality13. In this context, a self-selected exercise intensity (SSI) has been proposed as a possible approach strategy to increase adherence15. Self-selected intensity (SSI)16 is characterized by the control of intensity by the participant, he/she being free to choose and adjust the exercise intensity during the training sessions17. In addition, in recent years, SSI has gained greater recognition and is being applied in the treatment of obesity17. Therefore, it is important to investigate whether there is a difference in sleep parameters between aerobic training with a self-selected or predetermined intensity in adolescents with obesity.Of note, adherence to physical activity programs is one of the major challenges for obesity treatmentThus, the purpose of this study was to compare the effects of self-selected and predetermined intensity on sleep quality and duration, daytime sleepiness, and sleep efficiency of adolescents with obesity after 12 weeks of aerobic training. Our hypothesis was that both prescription strategies (self-selected and predetermined intensity) would improve sleep parameters in this population.18.This is a randomized clinical trial with two parallel groups and pre- and post-intervention evaluations. The outcomes presented here were part of a clinical trial that aimed to compare the effects of self-selected intensity and predetermined intensity exercise on health-related quality of life in adolescents with obesity, after 12 weeks of aerobic training , the results of which have been previously publishedth for age and sex19, within Tanner Stages 3-420, reported no restrictions to physical exercise , and agreed to participate in a regular exercise program. Exclusion criteria were: individuals with self-reported genetic, metabolic, or endocrine diseases, who were using medications that could modulate the outcomes , or were pregnant during the intervention.Adolescents from both sexes were recruited through local and social media advertisements and included if they met the following criteria: aged 13-18 years, BMI > 9518. Adolescents assigned to the SIG were instructed to choose their training intensity, for which the following verbal instruction was given at the beginning of every session: “select the intensity/speed at which you think you will be able to complete 35 minutes of exercise; however, you can modify the intensity/speed every 5 minutes”. In both groups, during all sessions, adolescents wore a heart rate monitor . The final assessments were realized in the end of the last exercise session.The adolescents performed the aerobic exercise on a treadmill, three times per week on alternate days, for 12 weeks. The training sessions were conducted in the morning or in the afternoon. And were divided into: five minutes of warm-up at 4.0 km/h, 25-minutes of training in their respective group, and five minutes of cool-down at 4.0 km/h. Adolescents assigned to the PIG trained at 60-70% of heart rate (HR) reserve during the main part of the protocol21. BMI was calculated using the standard formula (weight [kg]/height2 [m]) and plotted on charts to verify the percentile for age and sex19. Tanner’s stages were collected via self-assessments by the adolescents22.Body mass was measured to the nearest 0.1kg with a digital scale , and stature was measured to the nearest 0.5cm using a portable stadiometer , with the participants barefoot, with feet together, and head in the Frankfurt horizontal plane, wearing light clothing 23 and good test-retest reliability (r = 0.85)24. The PSQI measures the sleep habits in the previous month and is composed of 19 questions divided into seven domains . The final score ranges from zero to 21, with high values indicating poor sleep quality or sleep disorder. Total sleep duration was assessed by the fourth question of the PSQI “how many hours of actual sleep do you get at night”. Sleep efficiency is the percentage of time spent asleep while in bed, calculated by dividing the amount of time spent asleep (in minutes) by the total amount of time in bed (in minutes)25.Sleep quality and duration were assessed using the Pittsburgh Sleep Quality Index (PSQI), which has previously been validated for Brazilian adolescents with high internal consistency (α = 0.83)27. The ESS is a self-administered questionnaire that quantifies an individual’s propensity to fall asleep during eight routine situations: 1-Sitting and reading; 2-Watching TV; 3- Sitting, inactive in a public place; 4- As a passenger in a car for an hour without a break; 5- Lying down to rest in the afternoon when circumstances permit; 6- Sitting and talking to someone; 7-Sitting quietly after a lunch without alcohol; 8- In a car, while stopped for a few minutes in the traffic. The ESS final score ranges from zero to 24 points and higher values (≥10 points) indicate excessive daytime sleepiness.The Epworth Sleepiness Scale (ESS) was used to assess the daytime sleepiness of the adolescentsFor the present study, block randomization was used (randomizer.org). Boys and girls were randomized separately, generating the same ratio of girls/boys per group. Researchers were blinded to group assignment.28. An α value of ≤ 0.05 was used to signify statistical significance. Statistical analyses for all exercise data were performed using SPSS® software, version 21.0 , and Graph-Pad Prism version 5.0.The normality and homogeneity of the data were confirmed by the Shapiro-Wilk and Levene’s tests, respectively. Potential interaction factors  were evaluated using ANOVA models. As no statistically significant interactions were found, all sex and age groups were analyzed together. Intergroup (PIG vs SIG) differences in changes in the PSQI, sleep duration, and ESS scores from pre- to post-intervention were performed through calculating the absolute changes for each score (Δ= post-intervention – pre-intervention), and differences were evaluated using independent sample t-tests. Effect size (Cohen’s d) was used for both groups, PIG and SIG, after the intervention. Cohen’s d effect sizes were classified as trivial (d< 0.20), small (d = 0.20-0.49), moderate (d = 0.50-0.79), or large (d> 0.80) The intervention started with 37 adolescents  however, 12 participants dropped out (7 in PIG and 5 in SIG) and were not included in the analyses. The dropouts occurred in the familiarization week (n = 1); 4th-week (n = 1); 5th-week (n = 3); 7th-week (n = 2); and 8th-week (n = 3). The reasons for discontinuing were depression (n = 2); living too far away from the location of the training session (n = 5); lack of motivation (n = 3); and lack of time due to school schedules (n = 2). Two adolescents were excluded from the analysis because they had incomplete sleep data. The flowchart of the study is presented in The power of the analyzes was calculated (using G*Power v.3.1®), taking into account the sample size at the end of the intervention, and the effect size for the primary outcome variable (PSQI /d=0.60), and the value found for power was 0.99No baseline differences were observed for age, anthropometry, sleepiness, and sleep efficiency except for the PSQI for which the PIG presented higher values than the SIG (p=0.03) . OverallAfter 12-weeks of aerobic training, no differences were observed for PSQI , sleep duration , ESS , and sleep efficiency [ on sleep quality and have found mixed results31, however, the regular practice of exercise by normal-weight adolescents is associated with a perception of good sleep quality32. Previous reviews34, showing the impact of exercise on sleep have been most frequently expressed in terms of post-exercise changes in sleep-stages, with increases in levels of exercise leading to greater duration and intensity of stage 3 sleep. Despite the certainty about the beneficial small effects of exercise in other populations10, studies exploring the role of exercise in adolescents with obesity (body mass index: 34.0 ± 4.7 kg/ m2) are scarce, with only one found to date8.Adolescence and obesity are associated with physiological and behavioral changes that affect sleep patterns, especially sleep quantity and quality18. Heart rate variability is just one of the physiological responses to exercise that often presents changes and has been shown to have a direct effect on sleep quality 35. However, in the present study, it was observed that both groups worked at the same intensity. In a study by Vincent, Barnett (2017)36, light, moderate, and vigorous-intensity physical activity were measured by accelerometers in primary school-aged children. No significant associations were observed between time in bed, total sleep time, and sleep efficiency in any of the directions. Although that study had similar results to the current study, it was performed with school-aged children, whereas the present study was performed with adolescents with obesity.In the present study, the PIG performed training exclusively between 60%–70% of their HR reserve, and both groups exercised at 60-80% of their maximum HR, as has been previously published elsewhere38. However, these adjustments appear to be dependent on the intensity of the physical effort performed. In adolescents, the results of earlier studies appear contradictory and do not present a consensus, as some report better results in response to exercise at low-intensity40, others at high intensity37, and some report no differences in effects between the intensities on the outcome variable41.In a multidisciplinary context, aerobic training has been shown to be an effective and safe feature in the management of obesity and metabolic risksIn the present study, although no significant differences were observed between groups, the adherence to the experimental protocol was 62.1 %, representing moderate adherence to the protocol and this fact could increase the range of variation within the sample and influence better comparisons. However, from a clinical point of view, the aerobic training in the PIG and SIG was effective in promoting a reduction in PSQI and daytime sleepiness scores, when considering the individual responses.25. A sleep efficiency lower than 85 percent is considered poor and is a sign that an individual needs to get more efficient sleep. In hindsight, this might have been due to the other academic and social demands on these adolescents during the period of the intervention. It is important to highlight that, all of our experimental interventions were conducted between August and December; however, we recognize there could be some very important differences in this period of the year because most of the participants were sitting their final school exams, which may lead to changes in the routine of sleep.Although both groups showed a reduction in sleep time duration, sleep efficiency did not change significantly. A sleep efficiency of 85 percent or higher is considered to be normal, while a sleep efficiency anywhere above 90 percent is considered to be very good 42. In addition, among exercise characteristics, longer durations of individual exercise bouts resulted in greater reductions in sleep onset latency and greater adherence to the exercise training regimen was associated with greater improvement in sleep quality, whereas a longer duration of the exercise regimen was associated with smaller improvement in total sleep time10.Multiple studies have evaluated whether maintaining an exercise training regimen for a sustained duration of time  improves sleep. Unfortunately, similar to studies focused on acute exercise and sleep, until recently most exercise training studies focused on individuals with relatively normal sleep patterns at baseline; as one might expect, these studies demonstrated only mild, if any, sleep improvements following exercise training43. For instance, Kjeldsen et al. (2012) observed that only adults with obesity  submitted to high daily doses of aerobic exercise  presented increased sleep duration after 13 weeks, and moderate doses  did not alter sleep duration or quality. Similarly, Quist et al. (2019), compared groups of overweight and obese , adults at self-selected, moderate (50% VO2 peak-reserve), and vigorous intensity (70% VO2 peak-reserve) and reported that only the group that exercised at the higher intensity presented increased sleep duration, and none of the groups demonstrated improved sleep quality or sleepiness after 12 weeks of intervention. Furthermore, at 12 weeks, sleep quality scores were greater in the vigorous-intensity group compared to moderate and self-selected intensity11.However, interestingly, protocols of aerobic exercise at moderate intensity did not increase sleep duration or sleep quality in overweight and obese adults which is in agreement with the results of our research11. The intensity of exercise can play a fundamental role in homeostatic sleep and can lead to metabolic alterations in the brain that can improve the homeostatic regulation11. Previous studies with normal-weight adolescents show that high intensities can improve slow-wave sleep34. In addition, there is a theoretical model about energy conservation and body restoration, hypothesizing an increased need for sleep following exercise, thus a session leading to higher energy expenditure would have more impact on sleep patterns, such as duration and quality11.Therefore, there is a possibility that the relationship between aerobic exercise and sleep in individuals with obesity may be affected by greater volumes and intensities of exercise, which would result in greater energy expenditure2) to regular exercise exhibited improvements in sleep quality assessed by full night polysomnography and sleep duration recorded by an accelerometer8. However, it is worth mentioning that the authors used a protocol involving both aerobic and resistance exercise with a weekly volume of 240 minutes of exercise8. Our study used a protocol that comprises only 44% of the weekly volume that Mendelson et al., applied. Thus the improvements in sleep parameters seen by Mendelson et al., may be due to higher energy expenditures8.The only research submitting adolescents with obesity  in order to analyze the effects of exercise training on sleep architecture. Third, exercise sessions were conducted both in the morning and in the afternoon and whether the results would differ according to the time of the day deserves further investigation12. Although we had losses in the sample, the comparisons made did not differ significantly (p>0.05) from those considered in our analytical sample, and the losses occurred before the experimental protocol started, so a convenience sample was used. Certainly, these will be the objectives of a future study when we will have data from more volunteers available.The findings of the current study may have important practical applications. Adolescents commonly present sleep problems and these problems can be worsened with obesityThese results, although not statistically significant, provide evidence that working with predetermined or self-selected intensity in adolescents with obesity may be beneficial to better sleep quality, mainly when we consider the individual responses. However, as the slight differences are not statistically significant, the research results prove that regardless of predetermined or self-selected intensity, many parameters of sleep remain similar.In summary, the present study suggests that either self-selected or predetermined intensity of exercise does not modify the sleep quality, sleep duration, sleep efficiency, or daytime sleepiness of adolescents.


While there was no significant difference in body weight between the groups (p > 0.05), the NE group had a significantly higher exercise performance from weeks 2–14 (p < 0.01) and lower fat coefficient (p < 0.01) compared with the NC group. The Shannon index of the gut microbiota in the NC group was higher than that in the NE group at weeks 6 and 10, and the Chao1 index was higher than that in the NE group at week 14. Exercise performance positively correlated with the relative abundance of Phascolarctobacterium. Grouped time series data analysis demonstrated that Bifidobacteria, Coprococcus, and one unnamed genus in the Clostridiales order were significantly increased in the NE group, which correlated with increased glucose, flavonoid, arginine, and proline metabolism. In conclusion, moderate-intensity treadmill exercise significantly increased the exercise performance of mice and changed the core bacteria and bacterial metabolic activity. These results provide a reference for studying the effects of exercise intervention and exercise performance on the gut microbiota of mice.The gut microbiota is closely associated with the health of the host and is affected by many factors, including exercise. In this study, we compared the gut microbial changes and exercise performance over a 14-week period in mice that performed exercise  and mice that did not perform exercise . Mice were subjected to stool collection and exercise tests one week prior to adaptive training and after 2, 6, 10, and 14 weeks of exercise. Bacteria associated with the stool samples were assessed  The gut microbiota plays an essential role in human health  and is iThere is growing evidence that the gut microbiota can be modulated by various factors such as infection, antibiotics, diet, and exercise . ExercisExercise has been shown to improve both the physical and mental health of persons of any age , and is Thus, the purpose of our study was to determine if a 14-week, moderate-intensity exercise program could favorably modify the intestinal microbiota and influence the exercise performance of mice. The energy consumption of moderate-intensity exercise is 3–6 times higher than that of basic metabolism, and the intensity range is close to 40%–59% of the heart rate reserve or oxygen uptake reserve, 64%–76% of the maximum heart rate, and 46%–63% of the maximum oxygen uptake . In thisMost of the previous studies have focused on observing the changes in microbiota and metabolism after training , while tvia 16S rRNA sequencing.We compared the gut microbiota and exercise performance of mice subjected to no exercise or moderate-intensity exercise over a 14-week period. We collected stool and subjected both groups of mice to exercise performance tests at 5 different time points throughout the experiment, in addition to determining daily food intake and taking body weight measurements weekly. Bacteria associated with the stool samples were assessed Thirty specific pathogen-free C57BL/6 male mice  were purchased from the Guangdong Medical Experimental Animal Center . Upon arrival at our facility, the animals were housed in groups of 3–4 mice per cage in a room with a 12-hour light/dark cycle, an average temperature of 20–25°C, and relative humidity of 50–70%. The mice had access to water and regular chow  ad libitum. Components of the regular chow included corn, soybean meal, flour, wheat sub-meal, Peruvian fish meal, calcium hydrogen phosphate, stone powder, sodium chloride, vegetable oil, vitamins, amino acids, and minerals. All animal experiments were approved by the Scientific Research Ethics Sub-committee, School of Physical Education, South China Normal University  .After acclimating to the vivarium for two weeks, the mice were randomly divided into a control group (NC group) and exercise group (NE group), with 15 mice in each group. The food intake was calculated daily. The added food was weighed with an electronic balance  at 6 PM daily and 5 g of food was added per mouse per day. The next day, the remaining food was weighed and subtracted from the added amount, to determine the daily food intake. The mice were observed daily for signs of illness including a ruffled coat and injuries from fighting. Aggressive mice were separated into different cages, and open cuts from fighting were immediately cleaned with iodine  every day for a week. Injured mice were removed from the study. The mice were weighed at the same time every week.−1), followed by formal exercise training for 14 weeks. Formal exercise training was conducted with moderate-intensity treadmill exercise for 60 minutes a day, 5 days a week, with a slope of 0. The speed in weeks 1–2 was 14 m•min−1, the speed in weeks 3–6 was 15 m•min−1, the speed in weeks 7–10 was 17 m•min−1, and the speed in weeks 11–14 was 19 m•min−1. To eliminate the impact of other environmental factors on the results, the mice in the NC group were exposed to the same experimental environment during exercise training, but were not subjected to treadmill exercise.For the exercise intervention program, a rodent treadmill  was used. The mice in the NE group were subjected to adaptive treadmill exercise  with aseptic filter paper  on the bottom. A cotton swab was used to rub the abdomen and anus of the mice to stimulate defecation. Approximately five fecal pellets were collected from each mouse. Fecal pellets were collected with sterile forceps , placed in a sterile cryovial  (one pellet per tube), and stored on dry ice. All fecal pellets were stored at −80°C until future use.−1) for three consecutive days prior to each exercise performance test. The first exercise performance test for both the NC and NE groups occurred after the end of adaptation period. The other tests occurred at weeks 2, 6, 10, and 14 of the formal exercise intervention.To determine the exercise performance of mice, the longest running distance of exhaustive exercise was measured. The mice in both the NC and NE groups underwent a total of five exercise performance tests over the course of the experiment. Exercise performance tests were performed at the same time for both the NC and NE groups. Since mice in the NC group were not exposed to exercise training, these mice underwent adaptive training  DNA isolation kit . The quantity and quality of extracted DNA were measured using a NanoDrop ND-1000 spectrophotometer  and agarose gel electrophoresis, respectively.16S Amplicon Pyrosequencing: PCR amplification of the bacterial 16S rRNA genes V4 region was performed using the forward primer 515F (5’-GTGCCAGCMGCCGCGGTAA-3’) and the reverse primer 806R (5’-GGACTACHVGGGTWTCTAAT-3’). Sample-specific, paired-end, 6-bp barcodes were incorporated into the TrueSeq adaptors for multiplex sequencing. PCR amplicons were purified with Agencourt AMPure XP Beads  and quantified using the PicoGreen dsDNA Assay Kit . After the individual quantification step, amplicons were pooled in equal amounts, and pair-end 2 × 150 bp sequencing was performed using the Illlumina NovaSeq6000 platform at Hangzhou Guhe Information Technology Co., Ltd. . pipeline was employed to process the sequencing data.Sequence Analysis: The Quantitative Insights Into Microbial Ecology   pipelint test and the Monte Carlo permutation test with 1,000 permutations and were visualized via box-and-whiskers plots. Taxa abundances at the phylum, class, order, family, genus, and species levels were statistically compared among samples or groups via Kruskal test using the R stats package. Linear discriminant analysis effect size (LEfSe) was performed to detect differentially abundant taxa across groups using the default parameters of the linear discriminate analysis (LDA) score (default 2.0). The time intervals of the mutually differentially abundant genera from groups identified by METAgenomic LONgitudinal Differential Abundance method (MetaLonDA). Microbial functions were predicted by PICRUSt (Phylogenetic investigation of communities by reconstruction of unobserved states) based on high-quality sequences. In addition, a Pearson correlation analysis was conducted between exercise capacity and the relative abundance of bacteria. Correlation clustering analysis by hierarchical all-against-all association (HALLA) was used to discover significant relationships between data features at high power. The output file was further analyzed using Statistical Analysis of Metagenomic Profiles (STAMP) software package v2.1.3.Bioinformatics and Statistical Analysis: Sequence data analyses were mainly performed using the QIIME and R packages (v3.2.0). Operational taxonomic units (OTU)-level alpha diversity indices, such as Chao1 richness estimator, ACE metric, Shannon diversity index, and Simpson index, were calculated using the OTU table in QIIME. OTU-level ranked abundance curves were generated to compare the richness and evenness of OTUs among samples. Beta diversity analysis was performed to investigate the structural variation of the microbial communities. Principal coordinate analysis (PCoA) is a visualization method used to study the similarities or differences in data. PCoA can identify the most important coordinates in the distance matrix. The result is a rotation of the data matrix, which does not change the position relationship between the sample points . ThroughThe mice were euthanized 48 hours after the last exercise performance test. The mice were fasted 12 hours prior to euthanasia. The mice were weighed immediately before euthanizing, and the body length (distance from tip of nose to anus) of each mouse was measured afterwards. The mice were perfused with PBS, and then the epididymal fat, perirenal fat, groin fat, tibialis anterior muscle, gastrocnemius and quadriceps femoris were harvested, weighed, and snap-frozen in liquid nitrogen. The samples were stored at −80°C until future use.t test, repeated-measures ANOVA, rank-sum test, LEfSe, and MetaLonDA were used to compare groups, and correlation analysis was also conducted. p < 0.05 was considered statistically significant.The data were statistically analyzed using SPSS 20.0 software  and R. All data were expressed as mean ± standard deviation. Independent-sample The food intake and body weight of mice in both groups was measured over 14 weeks and analyzed using repeated-measures ANOVA Figure 1via Lee’s index. . Independent-sample t test was used to analyze the differences between the groups. There were no significant differences in body length, Lee’s index or muscle content between NE group and NC group . Over time, the exercise performance changed significantly. The interaction between time and group was significant , indicating that the exercise performance trend of different groups of mice was different. Simple-effects analysis showed no significant differences in the exercise performance of NC group between the time points. The exercise performance before intervention of NE group was significantly lower than that at other time points (p < 0.01). The exercise performance of NE group increased significantly at weeks 2 and 4, but not significantly from week 6. Before intervention, there was no significant difference in the exercise performance between NC and NE groups. However, from week 2, the exercise performance of NE group was significantly higher than that of NC group (p < 0.01) Figure 3http://qiime.org/). Chimeras were removed to obtain the effective sequences.The data was obtained in fastq format, and then the samples were paired and spliced into a single sequence. The sample corresponding to a sequence was determined by barcode, and the sequences were filtered by QIIME software , Firmicutes (31.80%), and Proteobacteria (3.03%). The relative abundance of these three phyla accounted for 97.97% of the total sequence. However, TM7, Actinobacteria, Verrucomicrobia, Tenericutes, undefined phylum, Cyanobacteria, Deferribacteres, and Thermi decreased Figure 5Lactobacillus (3.5%), Allobaculum (3.1%), Oscillospira (2.1%), Ruminococcus (1.8%), Coprococcus , Prevotella (5%), Bacteroides , and Desulfovibrio  (Lactobacillus (3.2%), Oscillospira (2.4%), Allobaculum (2.4%), Ruminococcus , Prevotella (5.2%), Bacteroides , Desulfovibrio , and Akkermansia , Allobaculum (3.7%), Ruminococcus (1.8%), Oscillospir (1.7%), Coprococcus , Prevotella (4.9%), Bacteroides , and Desulfovibrio  (The common dominant genera of each group were  phylum) Figure 6Lactobacillus, Dehalobacterium, Lac_[Ruminococcus], Rum_Ruminococcus, and Desulfovibrio in NC group were significantly higher than those in NE group . At week 2, the relative abundance of Dorea in NC group was significantly lower than that in NE group (p < 0.05); At week 6, the relative abundances of Dehalobacterium and Oscillospira in NC group were significantly higher than those in NE group (p < 0.05). At week 10, the relative abundance of Lactobacillus in NC group was significantly lower than that in NE group (p < 0.05), and the relative abundances of Oscillospira and Desulfovibrio in NC group was significantly higher than that in NE group (p < 0.05). At week 14, the relative abundances of Bacteroides, Parabacteroides, and Odoribacter in NC group were significantly higher than those in NE group (p < 0.05).Wilcoxon rank-sum test (BH-corrected) was used to compare the relative abundance of bacteria between the groups. The results showed that four phyla differed between the groups before intervention. The relative abundance of Bacteroidetes in NC group was significantly lower than that in NE group (p < 0.01), while the relative abundances of Firmicutes, Proteobacteria, and TM7 in NC group was significantly higher than that in NE group . At week 2, the relative abundance of Actinobacteria in NC group was significantly higher than that in NE group (p < 0.05), and at week 14, that in NC group was significantly lower than that in NE group (p < 0.05). Before intervention, there were five bacterial genera with differential relative abundance. The relative abundances of After determining that the sequencing depth was sufficient, we first evaluated the alpha diversity of the samples. Each index of alpha diversity was analyzed by Kruskal-wallis H-rank sum test. . The alpha diversity index with significant differences under different conditions was screened by rank sum test. The Shannon index, Simpson index, and Chao1 box chart of each group are shown in In addition, repeated-measures ANOVA was used to analyze changes in Shannon index in mice. The result of Mauchly’s test of sphericity showed p > 0.05. The tests of within-subjects effects showed that the main effect of time was significant . Over time, the Shannon index changed significantly. There was no significant interaction between time and group , suggesting that the Shannon index of different groups showed the same trend over time. The results of tests of between-subjects effects showed significant differences in Shannon index among different groups . Before intervention and at weeks 2 and 14, there were no significant differences between the groups, but at weeks 6 and 10, Shannon index of NC group was significantly higher than that of NE group .Repeated-measures ANOVA was used to analyze changes in Simpson index in mice. The result of Mauchly’s test of sphericity showed p < 0.05. The results of multivariate tests (Roy’s Largest Root) showed that the main effect of time was significant . There were significant differences in Simpson index between different time points. There was no significant interaction between time and group , indicating that the Simpson index of different groups showed the same trend over time. The results of tests of between-subjects effects showed that the groups differed in the Simpson index ; however, there was no significance difference among the time points (p > 0.05).Repeated-measures ANOVA was used to analyze changes in Chao1 index in mice. The result of Mauchly’s test of sphericity showed p < 0.05. The results of multivariate tests (Roy’s Largest Root) showed that the main effect of time was significant . There were significant differences in Chao1 index between different time points. There was no significant interaction between time and group , indicating that the Simpson index of different groups showed the same trend over time. The result of tests of between-subjects effects showed differences in the Chao1 index between the groups . Before intervention, and at weeks 2, 6, and 10, there were no significant differences between the groups, but at week 14, Chao1 index of NC group was significantly higher than that of NE group .2 = 0.3885, p = 0.06, F = 5.08, at the genera level .. Additionally, exercise has been shown to induce changes in the gut microbiome that are associated with parallel changes in host physiology . While studies have indicated that exercise-induced metabolic effects have the capacity to positively reshape the gut microbiota in various animal models and humans , changes to the structure of the gut microbiota varies depending on the intensity, time, and mode of exercise . Thus, the aim of our study was to determine if a 14-week, moderate-intensity exercise program could favorably modify the intestinal microbiota and influence the exercise performance of mice.Previous studies have demonstrated that exercise affects the gut microbiota and microbiome in rodents . Additisiology . While  humans , changexercise . Thus, Our initial results found no significant difference in food intake between the two groups during the entire experimental intervention period, except during the 2nd and 14th week. The NE group consumed significantly less food than the NC group during the 2nd week, but significantly more than the NC group during the 14th week. The initial decrease in food consumption of the NE group may be related to stress, as the mice may have been adapting to formal exercise training. The increase during the 14th week may represent an increase in the caloric needs of the NE mice compared with the NC group due to formal exercise. We found no significant difference in body weight between the two groups during the experimental intervention period.There were no significant differences in body length, Lee’s index or muscle content between the two groups, but the fat content in the NC group was significantly higher than that in the NE group. Hence, exercise can reduce fat accumulation, which is consistent with previous research results .Furthermore, after 14 weeks of moderate-intensity treadmill exercise intervention, the exercise performance of mice increased significantly, and there was a difference between the NE and NC groups after 2 weeks of the exercise intervention. These results indicate that the exercise intervention scheme used in this study is effective for improving the exercise performance of mice.In this study, we identified 11 phyla in the gut microbiota of the NE and NC groups. The three most abundant phyla in both groups were Bacteroidetes, Firmicutes, and Proteobacteria, which accounted for 97.97% of the total sequence. There were four differentially abundant phyla between the groups before intervention; these were Bacteroidetes, Firmicutes, Proteobacteria, and TM7. At week 2, the relative abundance of Actinobacteria in NC group was significantly higher than that in NE group, and at week 14, that in NC group was significantly lower than that in NE group. The effect of exercise intervention on phylum level was small, indicating that the gut microbiota was stable.Lactobacillus, Allobaculum, Oscillospira, Ruminococcus, and Prevotella. Before intervention, there were five differentially abundant bacterial genera, including Lactobacillus, Dehalobacterium, Lac_[Ruminococcus], Rum_Ruminococcus, and Desulfovibrio. At week 2, the relative abundance of Dorea in NC group was significantly lower than that in NE group. At week 6, the relative abundances of Dehalobacterium and Oscillospira in NC group was significantly higher than that in NE group. At week 10, the relative abundance of Lactobacillus in NC group was significantly lower than that in NE group, and the relative abundances of Oscillospira and Desulfovibrio in NC group were significantly higher than those in NE group. At week 14, the relative abundances of Bacteroides, Parabacteroides, and Odoribacter in NC group were significantly higher than those in NE group. The results showed that the microbiota changed at the phylum level and at the genus level during different intervention periods. Similarly, other studies have found changes in the microbiome composition of mice after exercise interventions. Exercise significantly changed the overall structure and composition of microbiota , the content of bacteria, such as Lactobacillus, Bifidobacterium , and Proteus . The amount of exercise  was inversely proportional to the ratio of Bacteroidetes to Firmicutes, and exercise greatly increased the proportion of butyric acid-producing bacteria in the intestines of mice  such as acetic acid, butyric acid, propionic acid, and lactic acid . Our research showed that exercise performance positively correlated with the relative abundance of Phascolarctobacterium. Phascolarctobacterium can produce SCFAs. SCFAs help certain species of microorganisms establish a dominant position in the microbiota and regulate glucose and lipid metabolism as signaling molecules. Additionally, SCFAs are primarily absorbed by intestinal epithelial cells and used for energy production. SCFAs also improve the intestinal pH and inhibit the growth of harmful bacteria such as indole-producing bacteria and hydrogen sulfide-producing bacteria within the intestinal tract .Since we were interested in understanding if exercise altered the core members of the gut microbiota, we used MetaLonDA to perform longitudinal analysis of the data. We found a significant time interval difference between the NC and NE groups. A total of 13 genera were significantly enriched in both groups, among which the abundance of mmation . Bifidoic acid . Our rel tract .via correlation cluster analysis that most of the enhanced metabolic activities, mainly glucose, flavonoid, arginine, and proline metabolism, were related to the increase in the three genera in the NE group. Since exercise is supported by energy provided by the metabolism of the host, it was not surprising that these metabolic pathways were identified as being intimately associated with exercise.Since exercise influenced the core members of the gut microbiota, we were interested in whether the metabolic activity of the gut microbiota was altered consequently. We found . Flavonoids have been shown to improve the level of oxidative stress in exercise-fatigued rats, inhibit body peroxidation during excessive exercise training, repair damaged cells, and promote metabolism. Increases in flavonoid metabolism are closely related to improvements in the antioxidant capacity of the body  can be found below: The animal study was reviewed and approved by School of Physical Education, South China Normal University .WY and YL: designing experiment. WY and GuangY: writing. ZY, GuanY, MC, and PH: data analysis. HW and XX: revising. YL and BM: project administrator. All authors contributed to the article and approved the submitted version.Funding for this study was received from Science and Technology Research Project of Hebei Sports Bureau (grant number: 20191020). Talent Introduction Special Funds of Lingnan Normal University to Yuqian Liu. (ZL2008) and Haitao Wang (ZL2009).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.


The treated cells were also characterised by diseased mitochondria, which is crucial for the survival of respiring cells, as observed by a significant (p < 0.05) loss of mitochondrial membrane potential (ΔΨM) and significant (p < 0.05) accumulation of reactive oxygen species (ROS) when compared to non-Rx cells. Moreover, the photolytic products of acetylsalicylic acid altered the ultrastructural appearance of treated cells as well as limited the expression levels of the capsular-associated gene, CAP64, when compared to non-Rx cells. The results of the study highlight the potential use of ASA as a photosensitiser that is effective for controlling the growth of cryptococcal cells. Potentially, this treatment can also be used as an adjuvant, to complement and support the usage of current anti-microbial agents. Photodynamic treatment (PDT) is often successful when used against aerobic microbes, given their natural susceptibility to oxidative damage. To this end, the current study aimed to explore the photodynamic action of acetylsalicylic acid , when administered to respiring cryptococcal cells. The treatment of cryptococcal cells, i.e., exposure to 0.5 or 1 mM of ASA in the presence of ultraviolet light (UVL) for 10 min, resulted in a significant ( Cryptococcus (C.) neoformans, is one of the most common opportunistic infections with a significant mortality rate among AIDS patients, more especially in resource-limited countries such as in sub-Saharan Africa -2H-tetrazolium hydroxide , 1 mM of menadione , germicidal ultraviolet light (UVL) lamp , Airstream® Class II Biological Safety Cabinet , SEM coating system , Shimadzu Superscan SSX 550 SEM  and Fluoroskan Ascent FL microplate reader .Yeast extract, malt extract, peptone, glucose, agar , phosphate buffer solution (PBS) , RPMI-1640 medium, foetal bovine serum , penicillin, streptomycin , C. neoformans LMPE 046 was used in this study. The strain was obtained from a patient at the Universitas Academic Hospital, Bloemfontein, South Africa. The strain was grown on yeast–malt-extract (YM) agar  at 37 °C for 48 h. Before use, 10 mL of phosphate buffer solution (PBS) was used to prepare standardised inocula with a final concentration of between 0.5 × 105 and 2.5 × 105 CFU/mL, according to the protocol of the European Committee on Antimicrobial Susceptibility Testing -2H-tetrazolium hydroxide  with 1 mM of menadione  were reacted with the cells. After three hours of incubation in the dark in a 5% CO2 incubator, which allowed the initiation of the tetrazolium reaction, the optical density (OD) was measured at 492 nm using a Biochrom spectrophotometer [The seeded macrophages  for 10 min, and the respective experimental condition being compared. For proper interpretation of the data, box plots were used, as recommended by Weissgerber et al., 2015 [For each study, three independent experiments were performed. No technical repeats were included for each independent experiment. Microsoft Excel was used to calculate mean values and the standard deviation of the means. The same programme was used to calculate the paired l., 2015 .This old technology of light therapy has provided us with some evidence for combating cryptococcal cells under controlled laboratory conditions. It will be interesting to see if similar results can be obtained in a diseased animal with a cryptococcal skin infection; additionally, to determine if this treatment would be suitable for controlling facultative organisms, which can switch to anaerobic glycolytic fermentative pathways. Given the effect of PDT with ASA on the health of macrophages , it would be prudent to now assess the impact of PDT with ASA on macrophage phagocytosis and to elucidate the molecular changes that may be enhanced to resolve internalised cells.The application of this form of treatment against internal cryptococcal infections may, at the moment, be limited by the lack of appropriate technology to deliver it to affected organs. However, hand-held devices can be used to resolve cutaneous cryptococcal infections. Care should also be taken to avoid continuous photoreactions, given the harmful effects of UV light on the skin, particularly when subjects have concluded PDT administration and are exposed to the sun’s radiation. To this end, it is equally important to show the benefit of this treatment when administered to skin epithelial cells. Such a study could also include a molecule that could modify how skin epithelial cells receive UV radiation. Additionally, there are already some topical creams that have salicylates as an ingredient available on the market ,49. The


Rhabdoviridae, Coronaviridae, and Paramyxoviridae. Viruses from these families have repeatedly spilled over to humans in recent decades, causing significant clinical disease and deaths. Here, metagenomic sequencing of a big brown bat (Eptesicus fuscus) submitted for rabies testing due to human exposure identified a novel paramyxovirus, Eptesicus fuscus orthorubulavirus (EfORV), in South Dakota, United States. The nearly complete 15,814-nucleotide genome shared 72% identity with that of human parainfluenza virus 4 (HPIV4), a virus that causes significant clinical disease, typically bronchiolitis and pneumonia, in children less than 2 years of age. Phylogenetic analysis confirmed a close evolutionary history between EfORV and HPIV4, reminiscent of other orthorubulaviruses with highly similar bat and mammalian species, including conspecific human and bat mumps virus, mammalian parainfluenza virus 5 and bat Alston virus, and porcine La Piedad Michoacán virus and bat Mapuera virus. These results support the idea that bats are a reservoir for diverse paramyxoviruses with closely shared evolutionary histories, compared with a number of significant human pathogens, and expand the range of bat paramyxoviruses to North America. Given the propensity of paramyxoviruses to overcome species barriers, additional surveillance and characterization of EfORV are warranted.Bats are a reservoir for many zoonotic viruses and host large numbers of genetically diverse species in the families IMPORTANCE Bats are a reservoir of large numbers of viruses. Among bat-borne zoonotic viruses, members of Coronaviridae and Paramyxoviridae have had the largest impact on human health. The repeated spillover of bat viruses to humans, often with devastating results, has led to increased surveillance and virus discovery efforts in hot spots for virus emergence, largely Asia and Africa. Apart from rabies virus, little surveillance of viruses in bats is performed in North America. Here, viral metagenomic sequencing identified a close relative to HPIV4 in a big brown bat found in a motel room in South Dakota. The virus, EfORV, was 72% identical to HPIV4, which causes clinically significant respiratory disease, mainly in children; it represents the first bat paramyxovirus identified in North America. Close genetic relationships between bat and mammalian orthorubulaviruses underscore the importance of bats as a reservoir for zoonotic viruses. Rhabdoviridae and Paramyxoviridae include bats as a reservoir for numerous species capable of zoonosis.Bats are an important reservoir for zoonotic viruses. In the nearly one century since the discovery of rabies virus in bats, a large number of clinically significant viruses have emerged from a bat reservoir , 2. RepeHenipavirus, emerged from bats in Australia and Malaysia, respectively  strain 6931. To our knowledge, this is the first bat paramyxovirus identified in North America.Despite the large amount of bat surveillance performed worldwide, comparably little surveillance has been performed in North America. In an effort to detect possible zoonotic viruses in synanthropic bats, metagenomic sequencing was performed on a tissue homogenate prepared from the viscera of a bat submitted for rabies testing. Direct fluorescent antibody testing of the brain yielded negative results for rabies virus. The bat was identified in a motel in central South Dakota and reportedly was crawling on the floor. A total of 852,138 paired-end 151-bp reads were used to assemble a 15,814-bp contig with 72.3% similarity to the orthorubulavirus HPIV4. The virus was named AAGAGGGGG-3′ (mRNA sense) located at nucleotide positions 2393 to 2401 leading to insertion of two nontemplated G residues and continuation of translation in an alternate reading frame. The remaining ORFs, for the M, F, HN, and L genes, code for 381, 544, 586, and 2,273 aa, respectively, which are 71.4, 58.2, 53.3, and 71.3% identical to those of HPIV4. An additional ORF, encoding 94 aa, was identified in the 475-nucleotide region between the M ORF and the F ORF. This ORF showed no homology to any proteins in the nonredundant database by BLASTP. Analysis of the transcriptional signals, however, failed to place the 94-aa-encoding ORF in the context of a transcriptional unit, suggesting that this gene is not expressed (Open reading frame (ORF) analysis identified canonical paramyxovirus genome organization. The partial N gene, encoding 551 amino acids (aa), was incomplete, missing approximately 6 aa based on sequence alignment with HPIV4b N, which was 74.9% identical. The nonstructural V gene was the second ORF and encodes a 218-aa protein with 37.3% identity to that of HPIV4b. The P gene, encoding a 391-aa protein with 42.7% identity to that of HPIV4b, shares its amino terminus with V, with a predicted RNA editing site of 5′-Paramyxoviridae resources page . Sequences were aligned by ClustalW, with phylogeny inferred by maximum-likelihood analysis using the best-fitting LG+G+I model of evolution; tree topology was assessed with 500 bootstrap replicates. EfORV occupied a sister clade closely related to that of HPIV4 -ATTGCTTCTCTTGCCCAAGTCCCA. Including the original sample, RNA was isolated from 90 bats that had been submitted for rabies testing. All bats were of the species Eptesicus fuscus; 84 originated from South Dakota, 5 from Minnesota, and 1 from Iowa. Eptesicus fuscus, commonly known as the big brown bat, is widespread throughout North America. The nonmigratory insectivorous bat commonly roosts in human structures, leading to frequent human exposure. The only positive sample was a submission in which EfORV was identified by sequencing (1/90 samples [1.1%]). South Dakota contains three distinct biomes, i.e., row crop and livestock agriculture in the eastern half of the state, with the western half being dominated by high plains grasslands and the coniferous Black Hills. The sample containing EfORV originated from the central high plains, from which our sample collection contained only two specimens. In addition to sampling biases, bat paramyxovirus shedding is periodic, with peak virus shedding occurring late in pregnancy and 2 months following parturition (To assess the prevalence of EfORV, a TaqMan assay was designed based on the L gene sequence, as follows: forward, 5′-turition . The batHPIV4 is a significant human pathogen. In the United States from 2011 to 2019, 2,700,135 HPIV tests were conducted for patients with respiratory disease. Five percent of those tests were positive, with a subset of 13% being positive for HPIV4 . In CanaMZ355765.The genome of EfORV strain 6931 was submitted to GenBank under accession number


Hit finding, scaffold hopping, and structure–activity relationship studies are important tasks in rational drug discovery. Implementation of these tasks strongly depends on the availability of compounds similar to a known bioactive molecule. SwissSimilarity is a web tool for low-to-high-throughput virtual screening of multiple chemical libraries to find molecules similar to a compound of interest. According to the similarity principle, the output list of molecules generated by SwissSimilarity is expected to be enriched in compounds that are likely to share common protein targets with the query molecule and that can, therefore, be acquired and tested experimentally in priority. Compound libraries available for screening using SwissSimilarity include approved drugs, clinical candidates, known bioactive molecules, commercially available and synthetically accessible compounds. The first version of SwissSimilarity launched in 2015 made use of various 2D and 3D molecular descriptors, including path-based FP2 fingerprints and ElectroShape vectors. However, during the last few years, new fingerprinting methods for molecular description have been developed or have become popular. Here we would like to announce the launch of the new version of the SwissSimilarity web tool, which features additional 2D and 3D methods for estimation of molecular similarity: extended-connectivity, MinHash, 2D pharmacophore, extended reduced graph, and extended 3D fingerprints. Moreover, it is now possible to screen for molecular structures having the same scaffold as the query compound. Additionally, all compound libraries available for screening in SwissSimilarity have been updated, and several new ones have been added to the list. Finally, the interface of the website has been comprehensively rebuilt to provide a better user experience. The new version of SwissSimilarity is freely available starting from December 2021. Drug discovery is unarguably a very complex, expensive, labor-intensive, and time-consuming endeavor. Therefore, considerable effort has been undertaken to facilitate and speed up the underlying processes. Notably, scientific progress in the field of protein structure elucidation as well as the development of computational methodologies stimulated the advent of rational drug discovery and virtual screening. The latter is an in silico technique to search within large chemical libraries for compounds that are likely to be active on a particular target. Virtual screening can be performed using either structural information about a target of interest  or about its known ligands . Structure-based virtual screening employs experimental or modeled protein 3D structures to search for compounds that have shape and other properties complementary to protein binding sites. On the other hand, ligand-based virtual screening searches for small molecules that are similar to the known active ligands, exploiting the similarity principle, which claims that similar compounds are prone to have similar bioactivities.http://www.swisssimilarity.ch) that provides a user-friendly interface for ligand-based virtual screening of chemical libraries, to find compounds that are similar to a query molecule. SwissSimilarity offers several compound libraries for screening, including approved drugs, known bioactive molecules, commercially available and synthetically accessible compounds. To calculate molecular similarity, SwissSimilarity proposes various 2D and 3D molecular fingerprints, which encode compounds in different digital formats, useful to quantify chemical similarity [SwissSimilarity is an online tool  DrugBank  that contains FDA-approved, experimental, investigational and withdrawn drugs, as well as illicit compounds and nutraceuticals ; (2) Ligwww.chemaxon.com, accessed on 19 December 2021). OpenBabel was used to convert molecules from SDF to SMILES format when needed and to remove duplicates. Filter-it was employed to remove molecules that have less than six heavy atoms or molecular weight more than 1500 g/mol and to keep compounds that contain only H, C, N, O, S, P, B, F, Cl, Br, and I in their largest fragment. Afterwards, the molecules were standardized , and their most frequent tautomeric state was generated using JChem Microservices. For 3D fingerprinting, the major protonation state at pH 7.4 was calculated by JChem Microservices and further submitted for conformers generation, which was achieved by RDkit  for E3FP fingerprints  , Filter-.1.1 , Fihttps://github.com/reymond-group/mhfp for MHFP6, version 1.9.2 and https://github.com/keiserlab/e3fp for E3FP, version 1.2.3, both repositories accessed on 19 July 2021). For E3FP generation, optimized parameters for fingerprinting were chosen [FP2 and ECFP with diameter 4 (ECFP4) were generated using OpenBabel (version 3.1.1) in the form of 2048-bit vectors. To enable screening of molecular structures having the same scaffold, Murcko  and genee chosen . In ordee chosen , while te chosen . To better understand and compare the meaning of the similarity values determined by different methods, we calculated the probability that two bioactive small molecules share a common protein target as a function of their similarity calculated using different molecular fingerprints/vectors. The dataset for calculating these probability curves consisted of 10 million pairs of compounds experimentally active on the same target (among 2261 proteins) and 100 million pairs of randomly selected compounds (presumably without a common target). Compounds and their interactions were retrieved from the ChEMBL25 database using the protocol described elsewhere .www.chemaxon.com, accessed on 19 December 2021); the attached MarvinJS Webservices further convert sketched molecular structures into SMILES. ChemAxon JChem Microservices (version 21.3) was also used to generate images of queries and similar molecules from their SMILES for the output page. The input query compound was prepared the same way as the screening libraries with the only exception that the most frequent tautomeric state was not generated for the query structure, to respect the choice of a user.The backend of the new SwissSimilarity website was written in Python 3.9, while its frontend was built using HTML5, PHP 7.4.3, and JavaScript. A queuing system, based on Slurm (version 19.05.5), was set up on the calculation server. This allows better control of the system and it increases the user’s comfort with possibilities to monitor the progress or to stop the computation. Users can provide a query molecule directly as SMILES or through the MarvinJS chemical editor  “Drugs” including approved, experimental and withdrawn drugs, as well as drug candidates that reached clinical trials; (2) “Bioactive” compounds including the LigandExpo collection containing small molecules that appear in the structure entries of the Protein Data Bank, the Chemical Entities of Biological Interest (ChEBI) collection, all compounds from the ChEMBL29 database, the GPCR–Ligand Association (GLASS) database, and the Human Metabolome Database; (3) “Commercial” compounds from vendor catalogs and from different ZINC subsets; (4) “Synthesizable” compounds that can be readily synthesized and provided by a shortlist of vendors. In particular, on top of ZINC , it is possible to screen compounds in the following commercially available chemical libraries: Enamine, ChemBridge, Maybridge, Asinex, AsisChem, Otava, SPECS, TimTec, Vitas, Life Chemicals, ChemDiv, and Innovapharm. Additionally, it is possible to perform searches in focused libraries containing biologically active compounds as well as GPCRs-, kinases- and proteases-targeting molecules. Several 2D and 3D methods are available to perform similarity searches using SwissSimilarity. Among 2D methods, users can opt for FP2 , ECFP4 , MHFP6 , 2D pharAlthough all similarity scores used in SwissSimilarity vary from 0, for totally dissimilar molecules, to 1, for identical compounds, they cannot be straightforwardly compared. Indeed, similarity values between a given couple of molecules can vary significantly depending on the method chosen for the similarity estimation. For instance, losartan and olmesartan, both Angiotensin receptor type I blockers, have Tanimoto coefficients of 0.72, 0.55, and 0.30 according to their FP2, ECFP4, and E3FP fingerprints, respectively. As a consequence, different similarity thresholds must be applied to these different methods to retrieve similar compounds. In order to define these thresholds, the probability that several molecules share the same protein target as a function of a given similarity value has been calculated for every method available in SwissSimilarity . The proDepending on the number of compounds in a chemical library, on the chosen screening method, and, to a lower extent, on the size and flexibility of the query molecule, the time required to perform the similarity search can vary greatly, from a second to ~20 min. Out of all available screening methods, FP2-, ECFP4-, and (generic) scaffold-based similarity searches provide the best performance in terms of speed, and they can be used to screen all available libraries in SwissSimilarity. In particular, screening of the largest library of 30 million tangible compounds provided by Enamine takes around 200 s with those methods. A queuing system was implemented in order to allow several submitted jobs to run in parallel. An approximate estimation of the computation time is provided on the website for each library/screening method combination to help users to choose the most appropriate options.www.google.com/chrome/, accessed on 19 December 2021) and Mozilla Firefox browsers . Outputs are provided under the CC-BY 4.0 license. To perform virtual screening using SwissSimilarity, users need to (1) provide a query molecule, (2) select a preferred class of compound libraries , and (3) choose a method and a library, in which the similarity search will take place (SwissSimilarity is freely accessible and no registration/log-in is required to use the website, which is optimized for recent versions of Google Chrome (ke place . By defake place . After pke place . The poske place . As alreThe updated version of the SwissSimilarity Web tool has been launched to incorporate novel approaches for molecular fingerprinting and provide access to updated chemical libraries. In addition, the SwissSimilarity interface has been greatly improved to achieve an enriched user experience. Virtual screening with SwissSimilarity is very easy: users only need to submit a reference compound and choose a preferred library/method combination. While the similarity principle is one of the main concepts in medicinal chemistry and chemoinformatics, SwissSimilarity is primarily intended for drug discovery scientists to support their hit-finding and scaffold-hopping activities, as well as studies addressing the structure–activity relationship. As part of the increasingly interoperable SwissDrugDesign project, SwissSimilarity further contributes to the development of a free, online environment for computer-aided drug design.