medRxiv - Epidemiology最新文献

{"title":"Obstructive sleep apnea mediates genetic risk of Diabetes Mellitus: The Hispanic Community Health Study/Study of Latinos","authors":"Yana Hrytsenko, Brian W. Spitzer, Heming Wang, Suzanne M. Bertisch, Kent Taylor, Olga Garcia-Bedoya, Alberto R. Ramos, Martha L. Daviglus, Linda C. Gallo, Carmen R. Isasi, Jianwen Cai, Qibin Qi, Carmela Alcantara, Susan Redline, Tamar Sofer","doi":"10.1101/2024.09.10.24313336","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313336","url":null,"abstract":"Objective: We sought to evaluate whether obstructive sleep apnea (OSA), and other sleep disorders, increase genetic risk of developing diabetes mellitus (DM). Research Design and Methods: Using GWAS summary statistics from the DIAGRAM consortium and Million Veteran Program, we developed multi-ancestry Type 2 Diabetes (T2D) polygenic risk scores (T2D-PRSs) useful in admixed Hispanic/Latino individuals. We estimated the association of the T2D-PRS with cross-sectional and incident DM in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We conducted a mediation analysis with T2D-PRSs as an exposure, incident DM as an outcome, and OSA as a mediator. Additionally, we performed Mendelian randomization (MR) analysis to assess the causal relationship between T2D and OSA. Results: Of 12,342 HCHS/SOL participants, at baseline, 48.4% were normoglycemic, 36.6% were hyperglycemic, and 15% had diabetes, and 50.9% identified as female. Mean age was 41.5, and mean BMI was 29.4. T2D-PRSs was strongly associated with baseline DM and with incident DM. At baseline, a 1 SD increase in the primary T2D-PRS had DM adjusted odds ratio (OR) = 2.67, 95% CI [2.40; 2.97] and a higher incident DM rate (incident rate ratio (IRR) = 2.02, 95% CI [1.75; 2.33]). In a stratified analysis based on OSA severity categories the associations were stronger in individuals with mild OSA compared to those with moderate to severe OSA. Mediation analysis suggested that OSA mediates the T2D-PRS association with DM. In two-sample MR analysis, T2D-PRS had a causal effect on OSA, OR = 1.03, 95% CI [1.01; 1.05], and OSA had a causal effect on T2D, with OR = 2.34, 95% CI [1.59; 3.44]. Conclusions: OSA likely mediates genetic effects on T2D. Keywords: Diabetes; Type 2 diabetes; Obstructive sleep apnea; Polygenic risk score; Hispanic or Latino","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Insomnia Symptoms and Trajectories with Incident Cardiovascular Disease: A Population-Based Cohort Study","authors":"Qing-Mei Huang, Hao-Yu Yan, Huan Chen, Jia-Hao Xie, Jian Gao, Zhi-Hao Li, Chen Mao","doi":"10.1101/2024.09.09.24313365","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313365","url":null,"abstract":"Background\u0000There is limited understanding regarding associations between insomnia symptoms, particularly the trajectories of insomnia symptoms, and cardiovascular disease (CVD). We aimed to investigate the associations of insomnia symptoms and trajectories with the risk of incident CVD. Methods This study used data from the Health and Retirement Study. Insomnia symptoms included non-restorative sleep, difficulty initiating sleep, early morning awakening, and difficulty maintaining sleep, classified on a scale ranging from 0 to 8. We also identified four distinct trajectories of insomnia symptoms: low, decreasing, increasing, and high insomnia symptoms. Examined outcomes included incident heart disease, stroke, and the combination of the two referred as CVD in the present study. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) after adjusting for potential confounders.\u0000Results A total of 12 102 participants aged 50 years or over without CVD at baseline were included. During a median follow-up of 10.2 years, 3 962 first CVD events occurred (3 372 heart disease and 1 200 stroke). Participants experiencing one (HR, 1.16 [95% CI, 1.05-1.27]), two (HR, 1.16 [ 95% CI, 1.05-1.28]), or three to four (HR, 1.26 [95% CI, 1.15-1.38]) insomnia symptoms had a higher risk of incident CVD compared to those not experiencing any insomnia symptoms. After a median follow-up of 8.4 years after the visit 2, 2 375 first CVD events occurred (1 981 heart disease and 705 stroke). Using the trajectory with low insomnia symptoms as the reference, increasing insomnia symptoms (HR, 1.28 [95% CI, 1.10-1.50]) and high insomnia symptoms (HR, 1.32 [95% CI, 1.15-1.50]) were associated with an increased risk of incident CVD. Conclusions Higher insomnia symptoms and increasing insomnia symptoms over time are associated with a higher risk of CVD in the community. Public health awareness and screening for insomnia symptoms in the middle-aged and elderly population should be encouraged to reduce CVD.\u0000Keywords\u0000Cardiovascular disease; Insomnia symptoms; Trajectory; Cohort study","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-infection dynamics of SARS-CoV-2 and respiratory viruses in the 2022/2023 respiratory season in the Netherlands","authors":"Gesa Carstens, Eva Kozanli, Kirsten Bulsink, Scott McDonald, Mansoer Elahi, Jordy de Bakker, Maarten Schipper, Rianne van Gageldonk-Lafeber, Susan van den Hof, Albert Jan van Hoek, Dirk Eggink","doi":"10.1101/2024.09.10.24313400","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313400","url":null,"abstract":"Objectives: Evaluation of the presence and effect of SARS-CoV-2 co-infections on disease severity. Methods: We collected both symptom data and nose- and throat samples from symptomatic people during the 2022/2023 respiratory season in a large participatory surveillance study in the Netherlands, and tested these for 18 respiratory viruses including SARS-CoV-2. We compared reported health status, symptoms and odds of having a mono respiratory viral infection or co-infection with SARS-CoV-2 and another respiratory virus. Results: In total 4,655 samples were included with 22% (n=1,017) testing SARS-CoV-2 positive. Of these 11% (n=116) also tested positive for a second respiratory virus. The most frequently occurring co-infections in SARS-CoV-2 positive participants were with rhinovirus (59%; n=69), seasonal coronaviruses (15%; n=17) and adenovirus (7%; n=8). Participants with a co-infection with one of these three viruses did not report more severe disease compared to those with a SARS-CoV-2 mono-infection. The odds of experiencing SARS-CoV-2 co-infection with seasonal coronavirus or rhinovirus were lower compared to the odds of the respective non-SARS-CoV-2 mono-infection (OR: 0.16, CI 95%: 0.10 - 0.24; OR: 0.21 CI 95%: 0.17 - 0.26; respectively). Conclusions: SARS-CoV-2 co-infections with rhinovirus, seasonal coronavirus and adenovirus are frequently observed in the general population, but are not associated with more severe disease compared to SARS-CoV-2 mono-infections. Furthermore, we found indications for inter-virus interaction with rhinovirus and seasonal coronavirus, possibly decreasing risk of co-infection.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collaborative forecasting of influenza-like illness in Italy: the Influcast experience","authors":"Stefania Fiandrino, Andrea Bizzotto, Giorgio Guzzetta, Stefano Merler, Federico Baldo, Eugenio Valdano, Alberto Mateo-Urdiales, Antonino Bella, Francesco Celino, Lorenzo Zino, Alessandro Rizzo, Yuhan Li, Nicola Perra, Corrado Gioannini, Paolo Milano, Daniela Paolotti, Marco Quaggiotto, Luca Rossi, Ivan Vismara, Alessandro Vespignani, Nicolo Gozzi","doi":"10.1101/2024.09.09.24313361","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313361","url":null,"abstract":"Collaborative hubs that integrate multiple teams to generate ensemble projections and forecasts for shared targets are now regarded as state-of-the-art in epidemic predictive modeling. In this paper, we introduce Influcast, Italy's first epidemic forecasting hub for influenza-like illness. During the 2023/2024 winter season, Influcast provided 20 rounds of forecasts, involving five teams and eight models to predict influenza-like illness incidence up to four weeks in advance at the national and regional administrative level. The individual forecasts were synthesized into an ensemble and benchmarked against a baseline model. The ensemble forecasts consistently outperformed both individual models and baseline forecasts, demonstrating superior accuracy at national and sub-national levels across various metrics. Despite a decline in absolute performance over longer horizons, the ensemble model outperformed the baseline in all considered time frames. These findings underscore the importance of multimodel forecasting hubs in producing consistent short-term influenza-like illnesses forecasts that can inform public health preparedness and mitigation strategies.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detecting imported malaria infections in endemic settings using molecular surveillance: current state and challenges","authors":"Mahdi Safarpour, Luis Esteban Cabrera Sosa, Dionicia Gamboa, Jean-Pierre Van geertruyden, Christopher Delgado-Ratto","doi":"10.1101/2024.09.09.24313136","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313136","url":null,"abstract":"The Global Technical Strategy for Malaria 2016 to 2030 targets eliminating malaria from at least 35 countries and reducing case incidence by 90% globally. The importation of parasites due to human mobilization presents a significant challenge to achieve elimination as it can undermine local interventions. A thorough understanding of importation is necessary to support efforts to control and further lead to elimination. Parasite genetic data is extensively deployed to investigate the space-time spread of imported infections. In this matter, this systematic review aimed to aggregate evidence on the use of parasite genetic data for mapping imported malaria and the statistical analytical methods. We discuss the advantages and limitations of the deployed genetic approaches and propose a suitable type of genetic data and statistical framework to discriminate imported malaria infections from local infections. The findings provide actionable insights for national control programs, helping them select the most suitable methods for detecting imported cases while supporting the evaluation of elimination program performance, particularly in low transmission settings.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiological profile of patients diagnosed with covid-19 in the municipality of Sao Goncalo, Rio de Janeiro, Brazil","authors":"Raphael Rangel das Chagas, Hercules Rezende Freitas, Sergian Vianna Cardozo","doi":"10.1101/2024.09.08.24313185","DOIUrl":"https://doi.org/10.1101/2024.09.08.24313185","url":null,"abstract":"Objectives: The global health crisis caused by SARS-CoV-2 has led to over 760 million confirmed cases and 6.8 million deaths worldwide, primarily impacting the respiratory system with symptoms varying from mild to severe. This study aimed to analyze the interplay between vaccination status, sociodemographic profiles, comorbidities, and COVID-19 outcomes.\u0000Study Design: Observational, cross-sectional, and analytical.\u0000Methods: The study analyzed data from 6,953 individuals, examining vaccination statuses, sociodemographic profiles, comorbidities, COVID-19 test results, and other relevant variables. The cohort comprised predominantly mixed-race (51%), Caucasian (38%), and Black (9.5%) individuals, with 61% being female and 60% aged between 21-50 years. Prevalent comorbidities included hypertension (18.2%), diabetes (4.9%), and obesity (0.4%).\u0000Results: Population-weighted analysis revealed significant associations between sociodemographic factors and COVID-19 test outcomes. Younger age groups, particularly 11-30 years, had higher positivity rates, which declined with age. Caucasians exhibited higher positivity rates (40.1%) compared to other ethnicities. Cramer's V indicated small correlations between symptoms and test outcomes, notably with loss of taste (V = 0.11) and smell (V = 0.08). Odds ratio analysis identified hypertension as significantly associated with higher COVID-19 positivity (OR = 1.54, 95% CI: 1.28-1.83, p < 0.001), while obesity was associated with lower positivity (OR = 0.13, 95% CI: 0.02-0.63, p = 0.025). Symptoms such as fever, cough, loss of taste, loss of smell, and myalgia also showed significant associations with positive test outcomes.\u0000Conclusions: This study provides valuable insights into the complex interplay of sociodemographic characteristics, comorbidities, symptoms, and COVID-19 outcomes.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accounting for partner notification in epidemiological birth-death-models","authors":"Anna ZHUKOVA, Olivier Gascuel","doi":"10.1101/2024.09.09.24313296","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313296","url":null,"abstract":"Phylodynamics bridges the gap between classical epidemiology and pathogen genome sequence data by estimating epidemiological parameters from time-scaled pathogen phylogenetic trees. The models used in phylodynamics typically assume that the sampling procedure is independent between infected individuals. However, this assumption does not hold for many epidemics, in particular for such sexually transmitted infections as HIV-1, for which partner notification schemes are included in health policies of many countries.\u0000We developed an extension of phylodynamic multi-type birth-death (MTBD) models with partner notification (PN), and a simulator to generate trees under MTBD and MTBD-PN models. We proposed a non-parametric test for detecting partner notification in pathogen phylogenetic trees. Its application to simulated data showed that it is both highly specific and sensitive. For the simplest representative of the MTBD-PN family, the BD-PN model, we solved the differential equations and proposed a closed form solution for the likelihood function. We implemented it in a program, which estimates the model parameters and their confidence intervals from phylogenetic trees. It performed accurate estimations on simulated data, and detected partner notification in HIV-1 B epidemics in Zurich and the UK. Importantly, we showed that not accounting for partner notification when it is present leads to bias in parameter estimation with the BD model, while BD-PN parameter estimator performs well both in presence and in absence of partner notification.\u0000Our PN test, MTBD-PN tree simulator and BD-PN parameter estimator are freely available at https://github.com/evolbioinfo/treesimulator and https://github.com/evolbioinfo/bdpn}{github.com/evolbioinfo/bdpn.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adapting COVID-19 research infrastructure to capture influenza and RSV alongside SARS-CoV-2 in UK healthcare workers winter 2022/23: Evaluation of the SIREN Winter Pressures pilot study","authors":"Katie Munro, Sophie Russell, Sarah Foulkes, Jonathan Broad, Dominic Sparkes, Ana Atti, Jasmin Islam, Susan Hopkins, Victoria Hall, SIREN study group","doi":"10.1101/2024.09.08.24313279","DOIUrl":"https://doi.org/10.1101/2024.09.08.24313279","url":null,"abstract":"Background: In 2022, with high early winter respiratory virus circulation, SIREN, a prospective healthcare worker cohort study monitoring SARS-CoV-2, ran a pilot study introducing multiplex PCR testing for SARS-CoV-2, influenza A/B, and RSV to investigate winter pressures. Three pathways were trialled: (A) on-site swabbing with local laboratory testing, (B) on-site swabbing with UKHSA-commissioned laboratory testing, and (C) postal swabbing with UKHSA-commissioned laboratory testing. Here, we compare pathways in relation to recruitment, testing coverage, participant acceptability, and UKHSA SIREN research team feedback.\u0000Methods: We conducted a mixed methods evaluation using metrics of quality assurance and study fidelity (participant recruitment and retention; multiplex PCR testing timing and coverage), an adapted NIHR ‘participant in research’ feedback questionnaire, and thematic analysis of a UKHSA SIREN research team workshop.\u0000Results: With 7,774 participants recruited, target recruitment (N=7,500) was achieved. Thirty-nine sites took part in the sub-study (4,289 participants). Thirty-three used pathway A, and six used pathway B. 3,485 participants enrolled to pathway C (27.8% of invitees). The median number of tests per participant was similar across pathways (6; 4; 5). However, sites using local laboratories showed a wide variation in the date they switched to multiplex testing (28th November 2022 to 16th March 2023). Consequently, influenza and RSV testing coverage was higher for pathways using UKHSA-commissioned laboratories (100.0% vs 45.6% at local laboratories). 1,204/7,774 (15.5%) participants completed the feedback survey. All pathways were acceptable to participants; 98.9% of postal and 97.5% of site-based participants ‘would consider taking part again’.\u0000Conclusion: Transitioning SARS-CoV-2 PCR testing to include influenza and RSV was challenging to achieve rapidly across multiple sites. The postal testing pathway proved more agile, and UKHSA-commissioned laboratory testing provided more comprehensive data collection than local laboratory testing. This sub-study indicates that postal protocols are effective, adaptable at pace, and acceptable to participants.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discriminatory ability of adiposity phenotypes in identifying cardiometabolic disorders in indigenous and non-indigenous African populations","authors":"Clement Nyuyki Kufe, Jean Claude Mbanya","doi":"10.1101/2024.09.07.24313232","DOIUrl":"https://doi.org/10.1101/2024.09.07.24313232","url":null,"abstract":"<strong>Background</strong> Whether any of the anthropometric indices are associated with cardiometabolic outcomes in indigenous Fulani African populations is not known. This study evaluates anthropometric indices in Fulani and non-autochthonous populations in predicting cardiometabolic outcomes in indigenous and non-indigenous populations.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of vaccination on SARS-CoV-2 transmission in the UK: a modelling study","authors":"Nieves Derqui, Swapnil Mishra, Wes R Hinsley, Samir Bhatt, Daniel J Laydon","doi":"10.1101/2024.09.06.24313210","DOIUrl":"https://doi.org/10.1101/2024.09.06.24313210","url":null,"abstract":"<strong>Background</strong> Efficacy and effectiveness of vaccines against SARS-CoV-2 infection, severe disease and death have been widely assessed. However, the impact of vaccination against SARS-CoV-2 transmission is far less well-characterized, and has major implications for public health, because it informs the indirect effects of vaccination in addition to its direct effects. Analysing the effects of SARS-CoV-2 vaccination on transmission is challenging, because they must be considered in tandem with the time-varying reproduction number (<em>R_t</em>), while also accounting for regional variability, for example due to the presence of more transmissible variants.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}