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Open accessJournal ArticleDOI: 10.1038/SREP21230

Correction: Corrigendum: The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes

23 Feb 2016-Scientific Reports (Nature Publishing Group)-Vol. 6, Iss: 1, pp 1-1
Abstract: Scientific Reports 5: Article number: 10942; published online: 01 June 2015; updated: 23 February 2016 This Article contains typographical errors in Table 2 where ‘Week 2 (N = 32)’ was incorrectly given as ‘Week (N = 2)’. more

Topics: Typographical error (50%)

Open accessJournal ArticleDOI: 10.1371/JOURNAL.PONE.0174944
Stephen Weng1, Jenna Reps1, Joe Kai1, Jonathan M. Garibaldi1  +1 moreInstitutions (1)
04 Apr 2017-PLOS ONE
Abstract: Background Current approaches to predict cardiovascular risk fail to identify many people who would benefit from preventive treatment, while others receive unnecessary intervention. Machine-learning offers opportunity to improve accuracy by exploiting complex interactions between risk factors. We assessed whether machine-learning can improve cardiovascular risk prediction. Methods Prospective cohort study using routine clinical data of 378,256 patients from UK family practices, free from cardiovascular disease at outset. Four machine-learning algorithms (random forest, logistic regression, gradient boosting machines, neural networks) were compared to an established algorithm (American College of Cardiology guidelines) to predict first cardiovascular event over 10-years. Predictive accuracy was assessed by area under the ‘receiver operating curve’ (AUC); and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) to predict 7.5% cardiovascular risk (threshold for initiating statins). Findings 24,970 incident cardiovascular events (6.6%) occurred. Compared to the established risk prediction algorithm (AUC 0.728, 95% CI 0.723–0.735), machine-learning algorithms improved prediction: random forest +1.7% (AUC 0.745, 95% CI 0.739–0.750), logistic regression +3.2% (AUC 0.760, 95% CI 0.755–0.766), gradient boosting +3.3% (AUC 0.761, 95% CI 0.755–0.766), neural networks +3.6% (AUC 0.764, 95% CI 0.759–0.769). The 78 highest achieving (neural networks) algorithm predicted 4,998/7,404 cases (sensitivity 79 67.5%, PPV 18.4%) and 53,458/75,585 non-cases (specificity 70.7%, NPV 95.7%), correctly predicting 355 (+7.6%) more patients who developed cardiovascular disease compared to the established algorithm. Conclusions Machine-learning significantly improves accuracy of cardiovascular risk prediction, increasing the number of patients identified who could benefit from preventive treatment, while avoiding unnecessary treatment of others. more

492 Citations

Open accessJournal ArticleDOI: 10.1002/ADMA.201806739
15 May 2019-Advanced Materials
Abstract: Disposable sensors are low-cost and easy-to-use sensing devices intended for short-term or rapid single-point measurements. The growing demand for fast, accessible, and reliable information in a vastly connected world makes disposable sensors increasingly important. The areas of application for such devices are numerous, ranging from pharmaceutical, agricultural, environmental, forensic, and food sciences to wearables and clinical diagnostics, especially in resource-limited settings. The capabilities of disposable sensors can extend beyond measuring traditional physical quantities (for example, temperature or pressure); they can provide critical chemical and biological information (chemo- and biosensors) that can be digitized and made available to users and centralized/decentralized facilities for data storage, remotely. These features could pave the way for new classes of low-cost systems for health, food, and environmental monitoring that can democratize sensing across the globe. Here, a brief insight into the materials and basics of sensors (methods of transduction, molecular recognition, and amplification) is provided followed by a comprehensive and critical overview of the disposable sensors currently used for medical diagnostics, food, and environmental analysis. Finally, views on how the field of disposable sensing devices will continue its evolution are discussed, including the future trends, challenges, and opportunities. more

Topics: Disposable Equipment (62%)

209 Citations

Open accessJournal ArticleDOI: 10.1080/07391102.2020.1760137
Rakesh Joshi1, Rakesh Joshi2, Shounak S. Jagdale2, Sneha B. Bansode2  +10 moreInstitutions (3)
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the current COVID-19 pandemic. Worldwide this disease has infected over 2.5 million individuals with a mortality rate ranging from 5 to 10%. There are several efforts going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (MPro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of MPro, we have performed phylogenetic and Sequence Similarity Network analysis, that depicted divergence of Coronaviridae MPro in five clusters specific to viral hosts. This clustering was corroborated with the comparison of MPro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. These attributes can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 MPro. In agreement with this, we performed screening of ∼7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 MPro as the primary target. We identified several natural molecules like δ-viniferin, myricitrin, taiwanhomoflavone A, lactucopicrin 15-oxalate, nympholide A, afzelin, biorobin, hesperidin and phyllaemblicin B that strongly binds to SARS-CoV-2 MPro. Intrestingly, these molecules also showed strong binding with other potential targets of SARS-CoV-2 infection like viral receptor human angiotensin-converting enzyme 2 (hACE-2) and RNA dependent RNA polymerase (RdRp). We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection.Communicated by Ramaswamy H. Sarma. more

Topics: Drug discovery (50%)

189 Citations

Open accessJournal ArticleDOI: 10.1111/IMM.12910
08 Mar 2018-Immunology
Abstract: Macrophages are extremely heterogeneous and plastic cells with an important role not only in physiological conditions, but also during inflammation (both for initiation and resolution). In the early 1990s, two different phenotypes of macrophages were described: one of them called classically activated (or inflammatory) macrophages (M1) and the other alternatively activated (or wound-healing) macrophages (M2). Currently, it is known that functional polarization of macrophages into only two groups is an over-simplified description of macrophage heterogeneity and plasticity; indeed, it is necessary to consider a continuum of functional states. Overall, the current available data indicate that macrophage polarization is a multifactorial process in which a huge number of factors can be involved producing different activation scenarios. Once a macrophage adopts a phenotype, it still retains the ability to continue changing in response to new environmental influences. The reversibility of polarization has a critical therapeutic value, especially in diseases in which an M1/M2 imbalance plays a pathogenic role. In this review, we assess the high plasticity of macrophages and their potential to be exploited to reduce chronic/detrimental inflammation. On the whole, the evidence detailed in this review underscores macrophage polarization as a target of interest for immunotherapy. more

Topics: Macrophage polarization (70%), Macrophage (52%)

158 Citations

Open accessJournal ArticleDOI: 10.1038/S41598-019-43195-6
30 Apr 2019-Scientific Reports
Abstract: Within mosquito vector populations, infectious mosquitoes are the ones completing the transmission of pathogens to susceptible hosts and they are, consequently, of great epidemiological interest. Mosquito infection by malaria parasites has been shown to affect several traits of mosquito physiology and behavior, and could interplay with the efficacy of control tools. In this study, we evaluated, in pyrethroid resistant Anopheles gambiae, the effect of mosquito infection with the human malaria parasite Plasmodium falciparum on the efficacy of nets treated with either the insecticide deltamethrin or the repellent DEET, measuring (i) mosquito success to pass through the net, (ii) blood-feeding on a host and (iii) chemicals-induced mortality. Infection of mosquitoes at non-infectious stage did not affect their success to pass through the net, to blood-feed, nor chemicals-induced mortality. At infectious stage, depending on replicates, infected mosquitoes had higher mortality rates than uninfected mosquitoes, with stronger effect in presence of DEET. This data evidenced a cost of infection on mosquito survival at transmissible stages of infection, which could have significant consequences for both malaria epidemiology and vector control. This stresses the need for understanding the combined effects of insecticide resistance and infection on the efficacy on control tools. Mosquito-borne diseases are considerable public health issues, mostly affecting populations in developing countries 1,2. To reduce their incidence, controlling vector mosquitoes and limiting their contact with human hosts remains the most effective strategy 3. One promising approach for achieving this goal would be to selectively target, within mosquito populations, individuals that are the most dangerous for humans 4. Particularly, mosquitoes carrying transmissible forms of pathogens in their salivary glands (i.e. infectious mosquitoes), are of great epidemiological relevance. Yet, the implementation of control means that could specifically reach infectious mosquitoes is dependent upon an extensive knowledge of the effects of mosquito infection on its behavior and physiology. Infection by pathogens has been shown to affect mosquito phenotypic traits 5. Malaria-infected Anopheles mosquitoes generally display increase attraction, biting and feeding rate 6-10. Interestingly, these changes are often concomitant with the presence of transmissible stages of the pathogen and may contribute to increase the number of contacts between human hosts and infectious vectors 11. These effects may lead to substantial epidemiological consequences, with transmission rates of mosquito borne pathogens being potentially much higher than expected 12. On the other hand, infection by malaria parasites may induce fitness costs on mosquitoes, reducing their survival. This can be especially true when infection is associated with other biotic and abiotic stresses 13-15. Consequently, all the behavioral and physiological changes associated with infection could directly impact the efficacy of control means. To date, conventional control tools mostly rely on the use of insecticide-treated nets (ITNs), although their efficacy could be threatened by the increase of insecticide resistance mechanisms in mosquito populations 16. Besides, repellents such as DEET (N, N-diethyl-3-methylbenzamide) offer a great potential both in cutaneous more

Topics: Anopheles gambiae (57%), Anopheles (55%), Malaria (53%) more

155 Citations


Journal ArticleDOI: 10.1097/00003246-198608000-00028
Abstract: This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status to provide a general measure of severity of disease. An increasing score (range 0 to 71) was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals. This relationship was also found for many common diseases.When APACHE II scores are combined with an accurate description of disease, they can prognostically stratify acutely ill patients and assist investigators comparing the success of new or differing forms of therapy. This scoring index can be used to evaluate the use of hospital resources and compare the efficacy of intensive care in different hospitals or over time. more

Topics: APACHE II (72%)

4,603 Citations

Open accessJournal ArticleDOI: 10.1056/NEJMOA1304459
Rongbao Gao1, Bin Cao2, Yunwen Hu, Zijian Feng1  +41 moreInstitutions (5)
Abstract: Background Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus. Methods We obtained and analyzed clinical, epidemiologic, and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase–polymerase-chain-reaction assays, viral culturing, and sequence analyses. Results A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) virus... more

1,985 Citations

Open accessJournal ArticleDOI: 10.1038/NM1477
01 Oct 2006-Nature Medicine
Abstract: Avian influenza A (H5N1) viruses cause severe disease in humans, but the basis for their virulence remains unclear. In vitro and animal studies indicate that high and disseminated viral replication is important for disease pathogenesis. Laboratory experiments suggest that virus-induced cytokine dysregulation may contribute to disease severity. To assess the relevance of these findings for human disease, we performed virological and immunological studies in 18 individuals with H5N1 and 8 individuals infected with human influenza virus subtypes. Influenza H5N1 infection in humans is characterized by high pharyngeal virus loads and frequent detection of viral RNA in rectum and blood. Viral RNA in blood was present only in fatal H5N1 cases and was associated with higher pharyngeal viral loads. We observed low peripheral blood T-lymphocyte counts and high chemokine and cytokine levels in H5N1-infected individuals, particularly in those who died, and these correlated with pharyngeal viral loads. Genetic characterization of H5N1 viruses revealed mutations in the viral polymerase complex associated with mammalian adaptation and virulence. Our observations indicate that high viral load, and the resulting intense inflammatory responses, are central to influenza H5N1 pathogenesis. The focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment. more

Topics: Viral load (66%), Viral pathogenesis (66%), Influenza A virus (63%) more

1,645 Citations

Open accessJournal ArticleDOI: 10.1016/S0140-6736(04)15595-5
Jsm Peiris1, W C Yu, C W Leung, CY Cheung1  +8 moreInstitutions (2)
21 Feb 2004-The Lancet
Abstract: Summary Human disease associated with influenza A subtype H5N1 reemerged in January, 2003, for the first time since an outbreak in Hong Kong in 1997. Patients with H5N1 disease had unusually high serum concentrations of chemokines (eg, interferon induced protein-10 [IP-10] and monokine induced by interferon γ [MIG]). Taken together with a previous report that H5N1 influenza viruses induce large amounts of proinflam-matory cytokines from macrophage cultures in vitro, our findings suggest that cytokine dysfunction contributes to the pathogenesis of H5N1 disease. Development of vaccines against influenza A (H5N1) virus should be made a priority. more

783 Citations

Open accessJournal ArticleDOI: 10.1016/S0140-6736(13)60903-4
Yu Chen1, Weifeng Liang1, Shigui Yang1, Nanping Wu1  +26 moreInstitutions (3)
01 Jun 2013-The Lancet
Abstract: Findings We identifi ed four patients (mean age 56 years), all of whom had contact with poultry 3–8 days before disease onset. They presented with fever and rapidly progressive pneumonia that did not respond to antibiotics. Patients were leucopenic and lymphopenic, and had impaired liver or renal function, substantially increased serum cytokine or chemokine concentrations, and disseminated intravascular coagulation with disease progression. T wo patients died. Sputum specimens were more likely to test positive for the H7N9 virus than were samples from throat swabs. The viral isolate from the patient was closely similar to that from an epidemiologically linked market chicken. All viral gene segments were of avian origin. The H7 of the isolated viruses was closest to that of the H7N3 virus from domestic ducks in Zhejiang, whereas the N9 was closest to that of the wild bird H7N9 virus in South Korea. We noted Gln226Leu and Gly186Val substitutions in human virus H7 (associated with increased affi nity for α-2,6-linked sialic acid receptors) and the PB2 Asp701Asn mutation (associated with mammalian adaptation). Ser31Asn mutation, which is associated with adamantane resistance, was noted in viral M2. Interpretation Cross species poultry-to-person transmission of this new reassortant H7N9 virus is associated with severe pneumonia and multiorgan dysfunction in human beings. Monitoring of the viral evolution and further study of disease pathogenesis will improve disease management, epidemic control, and pandemic preparedness. more

Topics: Virus (59%), Influenza A virus subtype H5N1 (57%), Human Virus (56%) more

749 Citations

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