{"title":"Pseudovirus technology in global health: A critical need for robust biosecurity measures","authors":"Abhijit Poddar , S.R. Rao","doi":"10.1016/j.jobb.2024.07.002","DOIUrl":"10.1016/j.jobb.2024.07.002","url":null,"abstract":"","PeriodicalId":52875,"journal":{"name":"Journal of Biosafety and Biosecurity","volume":"6 4","pages":"Pages 223-224"},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2588933824000384/pdfft?md5=e08b2d7d323a451bf516682ba068e063&pid=1-s2.0-S2588933824000384-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Auwal Rabiu Auwal , Isa Abdullahi Baba , Evren Hincal , Fathalla A. Rihan
{"title":"Computational modeling and inhibition of SARS-COV-2 Papain-like protease enzyme: A potential therapeutic approach for COVID-19","authors":"Auwal Rabiu Auwal , Isa Abdullahi Baba , Evren Hincal , Fathalla A. Rihan","doi":"10.1016/j.jobb.2024.07.001","DOIUrl":"10.1016/j.jobb.2024.07.001","url":null,"abstract":"<div><p>This study aims to investigate the potential impact of inhibitors targeting the papain-like protease (PLpro) of SARS-CoV-2 on viral replication and the host immune response. A mathematical model was developed to simulate the interaction among susceptible cells, infected cells, PLpro, and immune cells, incorporating data on PLpro inhibition. Through numerical simulations using MATLAB, the model parameters were estimated based on available statistical data. The results indicate that strategically positioned inhibitors could impede the virus’s access to host cellular machinery, thereby enhancing the immune response and gradually reducing susceptible and infected cells over time. The dynamics of the viral enzyme PLpro showed reduced activity with the introduction of the inhibitor, leading to a decline in viral replication. Moreover, the immune cell population exhibited functional recovery as the inhibitor suppressed PLpro activity. These findings suggest that inhibitors targeting PLpro may serve as therapeutic interventions against SARS-CoV-2 by inhibiting viral replication and bolstering the immune response.</p></div>","PeriodicalId":52875,"journal":{"name":"Journal of Biosafety and Biosecurity","volume":"6 3","pages":"Pages 211-221"},"PeriodicalIF":0.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2588933824000372/pdfft?md5=fdbf876165b0e2e2b70466ae5d584222&pid=1-s2.0-S2588933824000372-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iffatricia Haura Febiriana , Dipo Aldila , Bevina Desjwiandra Handari , Puji Budi Setia Asih , Muhamad Hifzhudin Noor Aziz
{"title":"Exploring the Interplay Between Social Awareness and the Use of Bed Nets in a Malaria Control Program","authors":"Iffatricia Haura Febiriana , Dipo Aldila , Bevina Desjwiandra Handari , Puji Budi Setia Asih , Muhamad Hifzhudin Noor Aziz","doi":"10.1016/j.jobb.2024.06.005","DOIUrl":"10.1016/j.jobb.2024.06.005","url":null,"abstract":"<div><p>This research aims to understand the effect of human awareness and the use of bed nets on malaria control programs. A deterministic host-vector mathematical model was utilized and simplified using the Quasi-Steady State Approximation, assuming the mosquito population is at equilibrium due to its fast, dynamic behavior. The model reveals two equilibrium states: the malaria-free equilibrium and the endemic equilibrium. The malaria-free equilibrium is locally asymptotically stable when the basic reproduction number is less than one and unstable if it is larger than one. Conversely, the malaria-endemic equilibrium is unique and stable if the reproduction number exceeds one and does not exist otherwise. Based on incidence data from Papua, parameter estimation and sensitivity analyses indicate that human awareness and the use of bed nets significantly reduce the reproduction number. To address budget constraints for interventions, the model was reformulated as an optimal control problem, characterized using the Pontryagin Maximum Principle, and solved with the forward–backward sweep method. Numerical experiments were conducted to assess the impact of various scenarios on the malaria control program. Cost-effectiveness analyses employing ACER, ICER, and IAR metrics suggest that while the combined implementation of awareness campaigns and bed nets effectively reduces infections, it incurs high costs. In contrast, implementing human awareness campaigns alone emerges as the best strategy based on ACER, ICER, and IAR standards. This study demonstrates that enhancing human awareness and promoting the use of bed nets are effective strategies for controlling malaria. However, due to budget constraints, focusing solely on awareness campaigns proves to be the most cost-effective intervention. This approach not only reduces malaria transmission but also optimizes resource allocation, highlighting the importance of targeted educational programs in public health initiatives for malaria control.</p></div>","PeriodicalId":52875,"journal":{"name":"Journal of Biosafety and Biosecurity","volume":"6 3","pages":"Pages 196-210"},"PeriodicalIF":0.0,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2588933824000359/pdfft?md5=286803da5b7a0c85dfa5ff19326db67a&pid=1-s2.0-S2588933824000359-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141690622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Abdurrahman Rois , Fatmawati , Cicik Alfiniyah , Santi Martini , Dipo Aldila , Farai Nyabadza
{"title":"Modeling and optimal control of COVID-19 with comorbidity and three-dose vaccination in Indonesia","authors":"Muhammad Abdurrahman Rois , Fatmawati , Cicik Alfiniyah , Santi Martini , Dipo Aldila , Farai Nyabadza","doi":"10.1016/j.jobb.2024.06.004","DOIUrl":"https://doi.org/10.1016/j.jobb.2024.06.004","url":null,"abstract":"<div><p>This paper presents and examines a COVID-19 model that takes comorbidities and up to three vaccine doses into account. We analyze the stability of the equilibria, examine herd immunity, and conduct a sensitivity analysis validated by data on COVID-19 in Indonesia. The disease-free equilibrium is locally and globally asymptotically stable whenever the basic reproduction number is less than one, while an endemic equilibrium exists and is globally asymptotically stable when the number is greater than one. Subsequently, the model incorporates two effective measures, namely public education and enhanced medical care, to determine the most advantageous approach for mitigating the transmission of the disease. The optimal control model is then determined using Pontryagin’s maximum principle. The integrated control strategy is the best method for reliably safeguarding the general population against COVID-19 infection. Cost evaluations and numerical simulations corroborate this conclusion.</p></div>","PeriodicalId":52875,"journal":{"name":"Journal of Biosafety and Biosecurity","volume":"6 3","pages":"Pages 181-195"},"PeriodicalIF":0.0,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2588933824000347/pdfft?md5=e3f237c1b54058dbee82e284d716e498&pid=1-s2.0-S2588933824000347-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141606860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laith N. AL-Eitan , Haneen O. Ali , Hana S. Abu Kharmah , Maryam K. Alasmar , Iliya Y. Khair , Ahmad H. Mihyar
{"title":"Addressing poxvirus challenges in the Middle East to enhance biosafety and biosecurity measures","authors":"Laith N. AL-Eitan , Haneen O. Ali , Hana S. Abu Kharmah , Maryam K. Alasmar , Iliya Y. Khair , Ahmad H. Mihyar","doi":"10.1016/j.jobb.2024.06.003","DOIUrl":"https://doi.org/10.1016/j.jobb.2024.06.003","url":null,"abstract":"<div><p>The emergence and zoonotic transmission of poxviruses in the Middle East have been recognized as complex public health issues. Poxviruses, a vast family of DNA viruses, can infect many hosts, including animals and humans. The Middle East has had multiple epidemics of poxvirus infections (e.g., Monkeypox, Smallpox, and Camelpox) that have raised concerns owing to their detrimental effects on livestock, wildlife, and sporadic human cases. This review aims to thoroughly examine the complexity of the epidemiological patterns, intricate genetic diversity, and several contributing factors that support the emergence and zoonotic transmission of poxviruses in the Middle East. Several aspects of poxviruses contribute to the emergence of endemics and zoonotic breakouts, such as the complex nature of human-animal interactions, environmental changes, and their subtle capacity for viral adaptability. This review was compiled in the hopes of contributing to the current understanding of poxvirus biology and its implications for human and animal health in the Middle East. We provide a comprehensive overview of the most common poxviruses in the Middle East, including their classification, structure, replication cycle, pathogenesis, route of transmissions, and of how the Middle East has developed ways to mitigate these biological threats.</p></div>","PeriodicalId":52875,"journal":{"name":"Journal of Biosafety and Biosecurity","volume":"6 3","pages":"Pages 142-156"},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2588933824000335/pdfft?md5=951f14f2c0d40a84ed4f933830b032c0&pid=1-s2.0-S2588933824000335-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141594908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nursanti Anggriani , Lazarus Kalvein Beay , Meksianis Z. Ndii , Fatuh Inayaturohmat , Sanubari Tansah Tresna
{"title":"A mathematical model for a disease outbreak considering waning-immunity class with nonlinear incidence and recovery rates","authors":"Nursanti Anggriani , Lazarus Kalvein Beay , Meksianis Z. Ndii , Fatuh Inayaturohmat , Sanubari Tansah Tresna","doi":"10.1016/j.jobb.2024.05.005","DOIUrl":"https://doi.org/10.1016/j.jobb.2024.05.005","url":null,"abstract":"<div><p>In the spread of infectious diseases, intervention levels play a crucial role in shaping interactions between healthy and infected individuals, leading to a nonlinear transmission process. Additionally, the availability of medical resources limits the recovery rate of infected patients, adding further nonlinear dynamics to the healing process. Our research introduces novelty by combining nonlinear incidence and recovery rates alongside waning immunity in an epidemic model. We present a modified SIRW-type model, examining the epidemic problem with these factors. Through analysis, we explore conditions for non-endemic and co-existing cases based on the basic reproduction ratio. The local stability of equilibria is verified using the Routh-Hurwitz criteria, while global stability is assessed using Lyapunov functions for each equilibrium. Furthermore, we investigate bifurcations around both non-endemic and co-existing equilibria. Numerically, we give some simulations to support our analytical findings.</p></div>","PeriodicalId":52875,"journal":{"name":"Journal of Biosafety and Biosecurity","volume":"6 3","pages":"Pages 170-180"},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2588933824000311/pdfft?md5=9a3f3ac37c5d275226798d8df28d62fc&pid=1-s2.0-S2588933824000311-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141594902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Salman Khalid Salman, Yasir Mufeed Abdulateef, Sawsan Qahtan Taha Al-Quhli
{"title":"The association between mycotic pneumonia and neonatal septicemia","authors":"Salman Khalid Salman, Yasir Mufeed Abdulateef, Sawsan Qahtan Taha Al-Quhli","doi":"10.1016/j.jobb.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.jobb.2024.06.002","url":null,"abstract":"<div><h3>Background</h3><p>Candida species are the fourth most common etiological agents of late-onset infection in the neonatal intensive care unit (NICU) and are responsible for considerable morbidity and mortality.</p></div><div><h3>Objectives</h3><p>From November 2023 to February 2024, we investigated the association of mycotic pneumonia with septicemia in 60 neonates, and their roles of mycotic pneumonia in the morbidity and mortality of neonates in two NICUs in the Al-Ramadi Teaching Hospital for Maternity and Children.</p></div><div><h3>Methods</h3><p>All infants in this study had been diagnosed with septicemia and treated with empirical antimicrobial therapy. An early morning nasogastric tube (NG-tube) was used to collect swallowed sputum by suction for culture and sensitivity testing.</p></div><div><h3>Results</h3><p>The average white blood count for the neonates was 8547 ± 5884.5 cells/mm<sup>2</sup>. The mean C-reactive protein was 39.3 ± 26 mg/l, the mean serum albumin was 2.9 ± 0.2 g/dl and the positive bacterial blood culture was 28 (46.7 %). 9 (15 %) neonates died during the study period. The NG-tube culture identified fungal growth in all samples. Of these, 49 (81.6 %) were identified as <em>Candida albicans</em>, 6 (10 %) as <em>Candida tropicalis</em>, and 5 (8.3 %) as <em>Cryptococcus laurentii</em>. The bacterial culture results from the NG-tube samples identified 13 (21.6 %) patients with gram-positive bacteria and 47 (78.3 %) with gram-negative bacteria.</p></div><div><h3>Conclusion</h3><p>We found a prevalence of Candida spp. among neonates in addition to microbial oxygen tube contamination, indicating a biosafety breach in the neonatal unit. Mycotic infection requires global attention as a probable cause of respiratory failure in neonatal septicemia.</p></div>","PeriodicalId":52875,"journal":{"name":"Journal of Biosafety and Biosecurity","volume":"6 3","pages":"Pages 137-141"},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2588933824000323/pdfft?md5=e98223a68d44a37acdaeed7c16c9e563&pid=1-s2.0-S2588933824000323-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141541035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ranjan K. Mohapatra , Ahmed Mahal , Pranab K. Mohapatra , Ashish K. Sarangi , Snehasish Mishra , Meshari A. Alsuwat , Nada N. Alshehri , Sozan M. Abdelkhalig , Mohammed Garout , Mohammed Aljeldah , Ahmad A. Alshehri , Ahmed Saif , Mohammed Abdulrahman Alshahrani , Ali S. Alqahtani , Yahya A. Almutawif , Hamza M.A. Eid , Faisal M Albaqami , Mohnad Abdalla , Ali A. Rabaan
{"title":"Structure-based discovery of F. religiosa phytochemicals as potential inhibitors against Monkeypox (mpox) viral protein","authors":"Ranjan K. Mohapatra , Ahmed Mahal , Pranab K. Mohapatra , Ashish K. Sarangi , Snehasish Mishra , Meshari A. Alsuwat , Nada N. Alshehri , Sozan M. Abdelkhalig , Mohammed Garout , Mohammed Aljeldah , Ahmad A. Alshehri , Ahmed Saif , Mohammed Abdulrahman Alshahrani , Ali S. Alqahtani , Yahya A. Almutawif , Hamza M.A. Eid , Faisal M Albaqami , Mohnad Abdalla , Ali A. Rabaan","doi":"10.1016/j.jobb.2024.05.004","DOIUrl":"https://doi.org/10.1016/j.jobb.2024.05.004","url":null,"abstract":"<div><p>Outbreaks of Monkeypox (mpox) in over 100 non-endemic countries in 2022 represented a serious global health concern. Once a neglected disease, mpox has become a global public health issue. A42R profilin-like protein from mpox (PDB ID: 4QWO) represents a potential new lead for drug development and may interact with various synthetic and natural compounds. In this report, the interaction of A42R profilin-like protein with six phytochemicals found in the medicinal plant <em>Ficus religiosa</em> (abundant in India) was examined. Based on the predicted and compared protein–ligand binding energies, biological properties, IC<sub>50</sub> values and toxicity, two compounds, kaempferol (C-1) and piperine (C-4), were selected. ADMET characteristics and quantitative structure–activity relationship (QSAR) of these two compounds were determined, and molecular dynamics (MD) simulations were performed. <em>In silico</em> examination of the kaempferol (C-1) and piperine (C-4) interactions with A42R profilin-like protein gave best-pose ligand-binding energies of –6.98 and –5.57 kcal/mol, respectively. The predicted IC<sub>50</sub> of C-1 was 7.63 μM and 82 μM for C-4. Toxicity data indicated that kaempferol and piperine are non-mutagenic, and the QSAR data revealed that piperlongumine (5.92) and piperine (5.25) had higher log P values than the other compounds examined. MD simulations of A42R profilin-like protein in complex with C-1 and C-4 were performed to examine the stability of the ligand–protein interactions. As/C and C-4 showed the highest affinity and activities, they may be suitable lead candidates for developing mpox therapeutic drugs. This study should facilitate discovering and synthesizing innovative therapeutics to address other infectious diseases.</p></div>","PeriodicalId":52875,"journal":{"name":"Journal of Biosafety and Biosecurity","volume":"6 3","pages":"Pages 157-169"},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S258893382400030X/pdfft?md5=ec15123379db8c297e57ae0d9b373a79&pid=1-s2.0-S258893382400030X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141594907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erratum regarding missing informed consents and ethic approval in previously published articles","authors":"","doi":"10.1016/j.jobb.2024.05.003","DOIUrl":"https://doi.org/10.1016/j.jobb.2024.05.003","url":null,"abstract":"","PeriodicalId":52875,"journal":{"name":"Journal of Biosafety and Biosecurity","volume":"6 2","pages":"Page 135"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2588933824000219/pdfft?md5=b67e62575b4a4adff1684815153d99af&pid=1-s2.0-S2588933824000219-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141541774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isa Abdullahi Baba , Fathalla A. Rihan , Evren Hincal
{"title":"Analyzing co-infection dynamics: A mathematical approach using fractional order modeling and Laplace-Adomian decomposition","authors":"Isa Abdullahi Baba , Fathalla A. Rihan , Evren Hincal","doi":"10.1016/j.jobb.2024.05.002","DOIUrl":"10.1016/j.jobb.2024.05.002","url":null,"abstract":"<div><p>The co-infection of HIV and COVID-19 is a pressing health concern, carrying substantial potential consequences. This study focuses on the vital task of comprehending the dynamics of HIV-COVID-19 co-infection, a fundamental step in formulating efficacious control strategies and optimizing healthcare approaches. Here, we introduce an innovative mathematical model grounded in Caputo fractional order differential equations, specifically designed to encapsulate the intricate dynamics of co-infection. This model encompasses multiple critical facets: the transmission dynamics of both HIV and COVID-19, the host’s immune responses, and the influence of treatment interventions. Our approach embraces the complexity of these factors to offer an exhaustive portrayal of co-infection dynamics. To tackle the fractional order model, we employ the Laplace-Adomian decomposition method, a potent mathematical tool for approximating solutions in fractional order differential equations. Utilizing this technique, we simulate the intricate interactions between these variables, yielding profound insights into the propagation of co-infection. Notably, we identify pivotal contributors to its advancement. In addition, we conduct a meticulous analysis of the convergence properties inherent in the series solutions acquired through the Laplace-Adomian decomposition method. This examination assures the reliability and accuracy of our mathematical methodology in approximating solutions. Our findings hold significant implications for the formulation of effective control strategies. Policymakers, healthcare professionals, and public health authorities will benefit from this research as they endeavor to curtail the proliferation and impact of HIV-COVID-19 co-infection.</p></div>","PeriodicalId":52875,"journal":{"name":"Journal of Biosafety and Biosecurity","volume":"6 2","pages":"Pages 113-124"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2588933824000207/pdfft?md5=5e953fc571289722d8dcd925b1ff0a92&pid=1-s2.0-S2588933824000207-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141032851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}