Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-30 (of 141 Records) |
Query Trace: Fan L[original query] |
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A compendium of multi-omics data illuminating host responses to lethal human virus infections
Eisfeld AJ , Anderson LN , Fan S , Walters KB , Halfmann PJ , Westhoff Smith D , Thackray LB , Tan Q , Sims AC , Menachery VD , Schäfer A , Sheahan TP , Cockrell AS , Stratton KG , Webb-Robertson BM , Kyle JE , Burnum-Johnson KE , Kim YM , Nicora CD , Peralta Z , N'Jai A U , Sahr F , van Bakel H , Diamond MS , Baric RS , Metz TO , Smith RD , Kawaoka Y , Waters KM . Sci Data 2024 11 (1) 328 Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For comparison, we have included transcriptomics datasets from cells treated with type I and type II human interferon. Raw multi-omics data and metadata were deposited in public repositories, and we provide a central location linking the raw data with experimental metadata and ready-to-use, quality-controlled, statistically processed multi-omics datasets not previously available in any public repository. This compendium of infection-induced host response data for reuse will be useful for those endeavouring to understand viral disease pathophysiology and network biology. |
Epitope(s) involving amino acids of the fusion loop of Japanese encephalitis virus envelope protein is(are) important to elicit protective immunity
Fan YC , Chen JM , Chen YY , Ke YD , Chang GJ , Chiou SS . J Virol 2024 e0177323 Dengue vaccine candidates have been shown to improve vaccine safety and efficacy by altering the residues or accessibility of the fusion loop on the virus envelope protein domain II (DII(FL)) in an ex vivo animal study. The current study aimed to comprehensively investigate the impact of DII(FL) mutations on the antigenicity, immunogenicity, and protective efficacy of Japanese encephalitis virus (JEV) virus-like particles (VLPs) in mice. We found the DII(FL) G106K/L107D (KD) and W101G/G106K/L107D (GKD) mutations altered the binding activity of JEV VLP to cross-reactive monoclonal antibodies but had no effect on their ability to elicit total IgG antibodies in mice. However, JEV VLPs with KD or GKD mutations induced significantly less neutralizing antibodies against JEV. Only 46% and 31% of the KD and GKD VLPs-immunized mice survived compared to 100% of the wild-type (WT) VLP-immunized mice after a lethal JEV challenge. In passive protection experiments, naïve mice that received sera from WT VLP-immunized mice exhibited a significantly higher survival rate of 46.7% compared to those receiving sera from KD VLP- and GKD VLP-immunized mice (6.7% and 0%, respectively). This study demonstrated that JEV DII(FL) is crucial for eliciting potently neutralizing antibodies and protective immunity against JEV. IMPORTANCE: Introduction of mutations into the fusion loop is one potential strategy for generating safe dengue and Zika vaccines by reducing the risk of severe dengue following subsequent infections, and for constructing live-attenuated vaccine candidates against newly emerging Japanese encephalitis virus (JEV) or Japanese encephalitis (JE) serocomplex virus. The monoclonal antibody studies indicated the fusion loop of JE serocomplex viruses primarily comprised non-neutralizing epitopes. However, the present study demonstrates that the JEV fusion loop plays a critical role in eliciting protective immunity in mice. Modifications to the fusion loop of JE serocomplex viruses might negatively affect vaccine efficacy compared to dengue and zika serocomplex viruses. Further studies are required to assess the impact of mutant fusion loop encoded by commonly used JEV vaccine strains on vaccine efficacy or safety after subsequent dengue virus infection. |
Low-temperature culture enhances production of flavivirus virus-like particles in mammalian cells
Fan YC . Appl Microbiol Biotechnol 2024 108 (1) 242 Flavivirus virus-like particles (VLPs) exhibit a striking structural resemblance to viral particles, making them highly adaptable for various applications, including vaccines and diagnostics. Consequently, increasing VLPs production is important and can be achieved by optimizing expression plasmids and cell culture conditions. While attempting to express genotype III (GIII) Japanese encephalitis virus (JEV) VLPs containing the G104H mutation in the envelope (E) protein, we failed to generate VLPs in COS-1 cells. However, VLPs production was restored by cultivating plasmid-transfected cells at a lower temperature, specifically 28 °C. Furthermore, we observed that the enhancement in JEV VLPs production was independent of amino acid mutations in the E protein. The optimal condition for JEV VLPs production in plasmid-transfected COS-1 cells consisted of an initial culture at 37 °C for 6 h, followed by a shift to 28 °C (37/28 °C) for cultivation. Under 37/28 °C cultivation conditions, flavivirus VLPs production significantly increased in various mammalian cell lines regardless of whether its expression was transiently transfected or clonally selected cells. Remarkably, clonally selected cell lines expressing flavivirus VLPs consistently achieved yields exceeding 1 μg/ml. Binding affinity analyses using monoclonal antibodies revealed similar binding patterns for VLPs of genotype I (GI) JEV, GIII JEV, West Nile virus (WNV), and dengue virus serotype 2 (DENV-2) produced under both 37 °C or 37/28 °C cultivation conditions. In summary, our study demonstrated that the production of flavivirus VLPs can be significantly improved under 37/28 °C cultivation conditions without affecting the conformational structure of the E protein. KEYPOINTS: • Low-temperature culture (37/28 °C) enhances production of flavivirus VLPs. • Flavivirus VLPs consistently achieved yields exceeding 1 μg/ml. • 37/28 °C cultivation did not alter the structure of flavivirus VLPs. |
A diverse group of small circular ssDNA viral genomes in human and non-human primate stools.
Ng TF , Zhang W , Sachsenröder J , Kondov NO , da Costa AC , Vega E , Holtz LR , Wu G , Wang D , Stine CO , Antonio M , Mulvaney US , Muench MO , Deng X , Ambert-Balay K , Pothier P , Vinjé J , Delwart E . Virus Evol 2015 1 (1) vev017 Viral metagenomics sequencing of fecal samples from outbreaks of acute gastroenteritis from the US revealed the presence of small circular ssDNA viral genomes encoding a replication initiator protein (Rep). Viral genomes were ∼2.5 kb in length, with bi-directionally oriented Rep and capsid (Cap) encoding genes and a stem loop structure downstream of Rep. Several genomes showed evidence of recombination. By digital screening of an in-house virome database (1.04 billion reads) using BLAST, we identified closely related sequences from cases of unexplained diarrhea in France. Deep sequencing and PCR detected such genomes in 7 of 25 US (28 percent) and 14 of 21 French outbreaks (67 percent). One of eighty-five sporadic diarrhea cases in the Gambia was positive by PCR. Twenty-two complete genomes were characterized showing that viruses from patients in the same outbreaks were closely related suggesting common origins. Similar genomes were also characterized from the stools of captive chimpanzees, a gorilla, a black howler monkey, and a lemur that were more diverse than the human stool-associated genomes. The name smacovirus is proposed for this monophyletic viral clade. Possible tropism include mammalian enteric cells or ingested food components such as infected plants. No evidence of viral amplification was found in immunodeficient mice orally inoculated with smacovirus-positive stool supernatants. A role for smacoviruses in diarrhea, if any, remains to be demonstrated. |
Assessing interventions to encourage primary care health workers to recommend influenza vaccination and the impact on vaccination uptake for persons with Non-Communicable diseases in China
Fan J , Song Y , Cong S , Millman AJ , Wang N , Greene C , Zhang R , Zhou S , Fang L . Vaccine 2024 BACKGROUND: Influenza vaccination coverage is low among persons with non-communicable diseases (NCDs) in China. Chinese health workers (HWs) do not routinely recommend influenza vaccination despite evidence that recommendations increase vaccine uptake. This study aims to assess whether interventions increased primary care HWs' recommendation for influenza vaccination and measure their impact on influenza vaccine uptake in persons with NCDs. METHODS: We conducted a cluster randomized controlled study in public primary healthcare clinics in Hubei from November 2018 through April 2019. In the intervention clinics, primary care HWs received training on the benefits of influenza vaccination and were asked to recommend influenza vaccine in routine primary healthcare for persons with NCDs. In the control clinics, primary care HWs did not receive training and provided standard services. We conducted questionnaire surveys before and after the intervention to collect information about recommendations made and receipt of influenza vaccines. RESULTS: A total of 896 primary care HWs and 4552 persons with NCDs were included. After intervention, a higher percentage of HWs recommended influenza vaccines in intervention clinics compared to control clinics. Vaccinated primary care HWs were more likely to recommend vaccination. Persons with NCDs reported higher influenza vaccination coverage in intervention than control clinics, and primary care HWs' recommendation increased vaccination uptake among persons with NCDs. CONCLUSIONS: Vaccinated primary care HWs were more likely to recommend influenza vaccination than unvaccinated HWs. Promoting primary care HWs' vaccination and encouraging them to recommend influenza vaccination during routine primary healthcare could increase influenza vaccine receipt among persons with NCDs. Registration number ChiCTR2200067140. |
Structural basis of the American mink ACE2 binding by Y453F trimeric spike glycoproteins of SARS-CoV-2
Ahn H , Calderon BM , Fan X , Gao Y , Horgan NL , Jiang N , Blohm DS , Hossain J , Rayyan NWK , Osman SH , Lin X , Currier M , Steel J , Wentworth DE , Zhou B , Liang B . J Med Virol 2023 95 (10) e29163 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2). While evolutionarily conserved, ACE2 receptors differ across various species and differential interactions with Spike (S) glycoproteins of SARS-CoV-2 viruses impact species specificity. Reverse zoonoses led to SARS-CoV-2 outbreaks on multiple American mink (Mustela vison) farms during the pandemic and gave rise to mink-associated S substitutions known for transmissibility between mink and zoonotic transmission to humans. In this study, we used bio-layer interferometry (BLI) to discern the differences in binding affinity between multiple human and mink-derived S glycoproteins of SARS-CoV-2 and their respective ACE2 receptors. Further, we conducted a structural analysis of a mink variant S glycoprotein and American mink ACE2 (mvACE2) using cryo-electron microscopy (cryo-EM), revealing four distinct conformations. We discovered a novel intermediary conformation where the mvACE2 receptor is bound to the receptor-binding domain (RBD) of the S glycoprotein in a "down" position, approximately 34° lower than previously reported "up" RBD. Finally, we compared residue interactions in the S-ACE2 complex interface of S glycoprotein conformations with varying RBD orientations. These findings provide valuable insights into the molecular mechanisms of SARS-CoV-2 entry. |
Investigating the associations between socioeconomic factors and unhealthy days among adults using zero-inflated negative binomial regression
Liu J , Jiang N , Fan AZ , Thompson WW , Ding R , Ni S . SAGE Open 2023 13 (3) Poor social and economic circumstances affect the health of individuals throughout the life cycle. The purpose of the study was to examine whether state-level and individual-level socioeconomic factors are associated with mentally or physically unhealthy days in the general U.S. population of adults. The Behavioral Risk Factor Surveillance System and the American Community Survey in 2016 were used to examine state-level social determinants of health and the number of self-reported mentally unhealthy days in the last 30 days using Zero-Inflated Negative Binomial (ZINB) regression models. Men, older individuals, minorities, persons with higher educational attainment levels, persons who were employed, persons who were married, or with a partner, and persons with one or zero chronic condition were more likely to report excessive zeros for responses to the mentally, and physically unhealthy days. The negative binomial regression results indicated that higher state-level poverty rates, higher income inequity, lower median income, and higher unemployment rates were related to the higher number of reported mentally, and physically unhealthy days. Persons with higher educational attainment, and who were employed reported lower mentally, and physically unhealthy days. The findings show significant relationships between socioeconomic contexts and general health status. Health planners and policymakers may use the results to allocate resources and guide public policies and programs. © The Author(s) 2023. |
SARS-CoV-2 susceptibility of cell lines and substrates commonly used in diagnosis and isolation of influenza and other viruses (preprint)
Wang L , Fan X , Bonenfant G , Cui D , Hossain J , Jiang N , Larson G , Currier M , Liddell J , Wilson M , Tamin A , Harcourt J , Ciomperlik-Patton J , Pang H , Dybdahl-Sissoko N , Campagnoli R , Shi PY , Barnes J , Thornburg NJ , Wentworth DE , Zhou B . bioRxiv 2021 2021.01.04.425336 Coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses is inevitable as the COVID-19 pandemic continues. This study aimed to evaluate cell lines commonly used in virus diagnosis and isolation for their susceptibility to SARS-CoV-2. While multiple kidney cell lines from monkeys were susceptible and permissive to SARS-CoV-2, many cell types derived from human, dog, mink, cat, mouse, or chicken were not. Analysis of MDCK cells, which are most commonly used for surveillance and study of influenza viruses, demonstrated that they were insusceptible to SARS-CoV-2 and that the cellular barrier to productive infection was due to low expression level of the angiotensin converting enzyme 2 (ACE2) receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by over-expression of canine ACE2 in trans. Moreover, SARS-CoV-2 cell tropism did not appear to be affected by a D614G mutation in the spike protein.Competing Interest StatementThe authors have declared no competing interest. |
N-glycosylation profiles of the SARS-CoV-2 spike D614G mutant and its ancestral protein characterized by advanced mass spectrometry (preprint)
Wang D , Zhou B , Keppel TR , Solano M , Baudys J , Goldstein J , Finn MG , Fan X , Chapman AP , Bundy JL , Woolfitt AR , Osman SH , Pirkle JL , Wentworth DE , Barr JR . bioRxiv 2021 2021.07.26.453787 N-glycosylation plays an important role in the structure and function of membrane and secreted proteins. The spike protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is heavily glycosylated and the major target for developing vaccines, therapeutic drugs and diagnostic tests. The first major SARS-CoV-2 variant carries a D614G substitution in the spike (S-D614G) that has been associated with altered conformation, enhanced ACE2 binding, and increased infectivity and transmission. In this report, we used mass spectrometry techniques to characterize and compare the N-glycosylation of the wild type (S-614D) or variant (S-614G) SARS-CoV-2 spike glycoproteins prepared under identical conditions. The data showed that half of the N-glycosylation sequons changed their distribution of glycans in the S-614G variant. The S-614G variant showed a decrease in the relative abundance of complex-type glycans (up to 45%) and an increase in oligomannose glycans (up to 33%) on all altered sequons. These changes led to a reduction in the overall complexity of the total N-glycosylation profile. All the glycosylation sites with altered patterns were in the spike head while the glycosylation of three sites in the stalk remained unchanged between S-614G and S-614D proteins.Competing Interest StatementThe authors have declared no competing interest. |
Comparison of Illumina MiSeq and the Ion Torrent PGM and S5 platforms for whole-genome sequencing of picornaviruses and caliciviruses (preprint)
Marine RL , Magana LC , Castro CJ , Zhao K , Montmayeur AM , Schmidt A , Diez-Valcarce M , Fan Ng TF , Vinje J , Burns CC , Allan Nix W , Rota PA , Oberste MS . bioRxiv 2019 705632 Next-generation sequencing is a powerful tool for virological surveillance. While Illumina® and Ion Torrent® sequencing platforms are used extensively for generating viral RNA genome sequences, there is limited data comparing different platforms. We evaluated the Illumina MiSeq, Ion Torrent PGM and Ion Torrent S5 platforms using a panel of sixteen specimens containing picornaviruses and human caliciviruses (noroviruses and sapoviruses). The specimens were processed, using combinations of three library preparation and five sequencing kits, to assess the quality and completeness of assembled viral genomes, and an estimation of cost per sample to generate the data was calculated. The choice of library preparation kit and sequencing platform was found to impact the breadth of genome coverage and accuracy of consensus viral genomes. The Ion Torrent S5 outperformed the older Ion Torrent PGM platform in data quality and cost, and generated the highest proportion of reads for enterovirus D68 samples. However, indels at homopolymer regions impacted the accuracy of consensus genome sequences. For lower throughput sequencing runs (i.e., Ion Torrent 510 or Illumina MiSeq Nano V2), the cost per sample was lower on the MiSeq platform, whereas with higher throughput runs (Ion Torrent 530 or Illumina MiSeq V2) the cost per sample was comparable. These findings suggest that the Ion Torrent S5 and Illumina MiSeq platforms are both viable options for genomic sequencing of RNA viruses, each with specific advantages and tradeoffs. |
Smart monitoring and control system test apparatus
Raj KV , Jacksha RD , Sunderman CB , Pritchard CJ . Trans Soc Min Metall Explor Inc 2018 344 (1) 62-66 In underground metal/nonmetal mines, repeated localized short-term exposure to high levels of airborne contaminants can become a serious health issue. Currently, there are no common mechanisms to control or mitigate these short-term high exposures to contaminants. To improve miners' health and safety, the U.S. National Institute for Occupational Safety and Health's Spokane Mining Research Division (SMRD) is developing a smart monitoring and control (SMAC) system for the real-time monitoring of mine air quality, with integrated countermeasures to reduce high concentrations of airborne contaminants in localized sections of mines. To develop and test a SMAC system capable of being implemented in an underground mine, SMRD researchers built a test apparatus incorporating a fan, louver, ducting and sensors combined with atmospheric monitoring and control software. This system will institute effective countermeasures to reduce contaminant levels, improving miner safety and health. |
SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility (preprint)
Zhou B , Thao TTN , Hoffmann D , Taddeo A , Ebert N , Labroussaa F , Pohlmann A , King J , Portmann J , Halwe NJ , Ulrich L , Trüeb BS , Kelly JN , Fan X , Hoffmann B , Steiner S , Wang L , Thomann L , Lin X , Stalder H , Pozzi B , de Brot S , Jiang N , Cui D , Hossain J , Wilson M , Keller M , Stark TJ , Barnes JR , Dijkman R , Jores J , Benarafa C , Wentworth DE , Thiel V , Beer M . bioRxiv 2020 During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic (1) . However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human ACE2, (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro , it provides a real competitive advantage in vivo , particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating. |
Molecular evolution and antigenic drift of type 3 iVDPVs excreted from a patient with immunodeficiency in Ningxia, China.
Fan Q , Ma J , Li X , Jorba J , Yuan F , Zhu H , Hu L , Song Y , Wang D , Zhu S , Yan D , Chen H , Xu W , Zhang Y . J Med Virol 2023 95 (1) e28215 A 2.5-year-old pediatric patient with acute flaccid paralysis was diagnosed with primary immunodeficiency (PID) in Ningxia Province, China, in 2011. Twelve consecutive stool specimens were collected from the patient over a period of 10 months (18 February 2011 to 20 November 2011), and 12 immunodeficiency vaccine-derived poliovirus (iVDPV) strains (CHN15017-1 to CHN15017-12) were subsequently isolated. Nucleotide sequencing analysis of the plaque-purified iVDPVs revealed 2%-3.5% VP1-region differences from their parental Sabin 3 strain. Full-length genome sequencing showed they were all Sabin 3/Sabin 1 recombinants, sharing a common 2C-region crossover site, and the two key determinants of attenuation (U472C in the 5' untranslated region and T2493C in the VP1 region) had reverted. Temperature-sensitive experiments demonstrated that the first two iVDPV strains partially retained the temperature-sensitive phenotype's nature, while the subsequent ten iVDPV strains distinctly lost it, possibly associated with increased neurovirulence. Nineteen amino-acid substitutions were detected between 12 iVDPVs and the parental Sabin strain, of which only one (K1419R) was found on the subsequent 10 iVDPV isolates, suggesting this site's potential as a temperature-sensitive determination site. A Bayesian Monte Carlo Markov Chain phylogenetic analysis based on the P1 coding region yielded a mean iVDPV evolutionary rate of 1.02 × 10(-2) total substitutions/site/year, and the initial oral-polio-vaccine dose was presumably administered around June 2009. Our findings provide valuable information regarding the genetic structure, high-temperature growth sensitivity, and antigenic properties of iVDPVs following long-term evolution in a single PID patient, thus augmenting the currently limited knowledge regarding the dynamic changes and evolutionary pathway of iVDPV populations with PID during long-term global replication. |
Efficacy of Do-It-Yourself air filtration units in reducing exposure to simulated respiratory aerosols
Derk RC , Coyle JP , Lindsley WG , Blachere FM , Lemons AR , Service SK , Martin SB Jr , Mead KR , Fotta SA , Reynolds JS , McKinney WG , Sinsel EW , Beezhold DH , Noti JD . Build Environ 2023 229 109920 Many respiratory diseases, including COVID-19, can be spread by aerosols expelled by infected people when they cough, talk, sing, or exhale. Exposure to these aerosols indoors can be reduced by portable air filtration units (air cleaners). Homemade or Do-It-Yourself (DIY) air filtration units are a popular alternative to commercially produced devices, but performance data is limited. Our study used a speaker-audience model to examine the efficacy of two popular types of DIY air filtration units, the Corsi-Rosenthal cube and a modified Ford air filtration unit, in reducing exposure to simulated respiratory aerosols within a mock classroom. Experiments were conducted using four breathing simulators at different locations in the room, one acting as the respiratory aerosol source and three as recipients. Optical particle spectrometers monitored simulated respiratory aerosol particles (0.3-3 μm) as they dispersed throughout the room. Using two DIY cubes (in the front and back of the room) increased the air change rate as much as 12.4 over room ventilation, depending on filter thickness and fan airflow. Using multiple linear regression, each unit increase of air change reduced exposure by 10%. Increasing the number of filters, filter thickness, and fan airflow significantly enhanced the air change rate, which resulted in exposure reductions of up to 73%. Our results show DIY air filtration units can be an effective means of reducing aerosol exposure. However, they also show performance of DIY units can vary considerably depending upon their design, construction, and positioning, and users should be mindful of these limitations. |
Impact of tenofovir disoproxil fumarate use during pregnancy on maternal bone mineral density
Wang L , Kourtis AP , Wiener J , Chen L , Liu W , Fan B , Shepherd J , Bulterys M . Pediatr Infect Dis J 2022 41 (12) 976-978 Chronic hepatitis B virus (HBV) infection and HIV infection are diseases of great public health importance. Tenofovir disoproxil fumarate (TDF), a nucleotide analog reverse transcriptase inhibitor, is effective for the treatment of both HIV and HBV.1,2 However, information on the bone safety of TDF during pregnancy, a time with increased demands on bone metabolism, has not been systematically assessed. | We conducted a phase II randomized controlled trial (RCT) in Guangxi Zhuang Autonomous Region of the People’s Republic of China, to evaluate the bone mineral density (BMD) effects of TDF on women and their infants. Effects of TDF on bone health of infants have been reported elsewhere3; this report presents our findings on the effects of TDF on maternal BMD. |
Investigating dilution ventilation control strategies in a modern U.S. school bus in the context of the COVID-19 pandemic.
Van Dyke M , King B , Esswein E , Adgate J , Dally M , Kosnett M . J Occup Environ Hyg 2022 19 (5) 1-16 Fresh air ventilation has been identified as a widely accepted engineering control effective at diluting air contaminants in enclosed environments. The goal of this study was to evaluate the effects of selected ventilation measures on air change rates in school buses. Air changes per hour (ACH) of outside air were measured using a well-established carbon dioxide (CO(2)) tracer gas decay method. Ventilation was assessed while stationary and while traversing standardized route during late autumn/winter months in Colorado. Seven CO(2) sensors located at the driver's seat and at passenger seats in the front, middle, and rear of the bus yielded similar and consistent measurements. Buses exhibited little air exchange in the absence of ventilation (ACH =0.13 when stationary; ACH =1.85 when mobile). Operating the windshield defroster to introduce fresh outside air increased ACH by approximately 0.5-1 ACH during mobile and stationary phases. During the mobile phase (average speed of 23 miles per hour (mph) ), the combination of the defroster and two open ceiling hatches (with a powered fan on the rear hatch) yielded an ACH of approximately 9.3 ACH. A mobile phase ACH of 12.4 was achieved by the combination of the defroster, ceiling hatches, and six passenger windows open 2 inches in the middle area of the bus. A maximum mobile phase ACH of 22.1 was observed by using the defroster, open ceiling hatches, driver window open 4 inches, and every other passenger window open 2 inches. For reference, ACHs recommended in patient care settings where patients are being treated for airborne infectious diseases range from 6 to ≥12 ACHs. The results indicate that practical ventilation protocols on school buses can achieve air change rates thought to be capable of reducing airborne viral transmission to the bus driver and student passengers during the COVID-19 pandemic. |
Distinguishing Multisystem Inflammatory Syndrome in Children From COVID-19, Kawasaki Disease and Toxic Shock Syndrome.
Godfred-Cato S , Abrams JY , Balachandran N , Jaggi P , Jones K , Rostad CA , Lu AT , Fan L , Jabbar A , Anderson EJ , Kao CM , Hunstad DA , Rosenberg RB , Zafferani MJ , Ede KC , Ballan W , Laham FR , Beltran Y , Bryant B , Meng L , Hammett TA , Oster ME , BamrahMorris S , Belay ED . Pediatr Infect Dis J 2022 41 (4) 315-323 BACKGROUND: Distinguishing multisystem inflammatory syndrome in children (MIS-C) from coronavirus disease 2019 (COVID-19), Kawasaki disease (KD), and toxic shock syndrome (TSS) can be challenging. Because clinical management of these conditions can vary, timely and accurate diagnosis is essential. METHODS: Data were collected from patients <21 years of age hospitalized with MIS-C, COVID-19, KD, and TSS in 4 major health care institutions. Patient demographics and clinical and laboratory data were compared among the 4 conditions, and a diagnostic scoring tool was developed to assist in clinical diagnosis. RESULTS: A total of 233 patients with MIS-C, 102 with COVID-19, 101 with KD, and 76 with TSS were included in the analysis. Patients with MIS-C had the highest prevalence of decreased cardiac function (38.6%), myocarditis (34.3%), pericardial effusion (38.2%), mitral regurgitation (31.8%) and pleural effusion (34.8%) compared with patients with the other conditions. Patients with MIS-C had increased peak levels of C-reactive protein and decreased platelets and lymphocyte nadir counts compared with patients with COVID-19 and KD and elevated levels of troponin, brain natriuretic peptide and pro-brain natriuretic peptide compared with COVID-19. Diagnostic scores utilizing clinical findings effectively distinguished MIS-C from COVID-19, KD, and TSS, with internal validation showing area under the curve ranging from 0.87 to 0.97. CONCLUSIONS: Compared with COVID-19, KD, and TSS, patients with MIS-C had significantly higher prevalence of cardiac complications, elevated markers of inflammation and cardiac damage, thrombocytopenia, and lymphopenia. Diagnostic scores can be a useful tool for distinguishing MIS-C from COVID-19, KD, and TSS. |
Associations Between Eight Earth Observation-Derived Climate Variables and Enteropathogen Infection: An Independent Participant Data Meta-Analysis of Surveillance Studies With Broad Spectrum Nucleic Acid Diagnostics.
Colston JM , Zaitchik BF , Badr HS , Burnett E , Ali SA , Rayamajhi A , Satter SM , Eibach D , Krumkamp R , May J , Chilengi R , Howard LM , Sow SO , JahangirHossain M , Saha D , ImranNisar M , Zaidi AKM , Kanungo S , Mandomando I , Faruque ASG , Kotloff KL , Levine MM , Breiman RF , Omore R , Page N , Platts-Mills JA , Ashorn U , Fan YM , Shrestha PS , Ahmed T , Mduma E , Yori PP , Bhutta Z , Bessong P , Olortegui MP , Lima AAM , Kang G , Humphrey J , Prendergast AJ , Ntozini R , Okada K , Wongboot W , Gaensbauer J , Melgar MT , Pelkonen T , Freitas CM , Kosek MN . Geohealth 2022 6 (1) e2021GH000452 Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens-adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia-was matched by date with hydrometeorological variables from a global Earth observation dataset-precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non-linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7-day average temperatures-a relative risk of 0.76 (95% confidence interval: 0.69-0.85) above 28C-while ETEC risk increased by almost half, 1.43 (1.36-1.50), in the 20-35C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower-than-average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea-causing agents as the global climate changes. |
Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta.
Ulrich L , Halwe NJ , Taddeo A , Ebert N , Schön J , Devisme C , Trüeb BS , Hoffmann B , Wider M , Fan X , Bekliz M , Essaidi-Laziosi M , Schmidt ML , Niemeyer D , Corman VM , Kraft A , Godel A , Laloli L , Kelly JN , Calderon BM , Breithaupt A , Wylezich C , Veiga IB , Gultom M , Osman S , Zhou B , Adea K , Meyer B , Eberhardt C , Thomann L , Gsell M , Labroussaa F , Jores J , Summerfield A , Drosten C , Eckerle IA , Wentworth DE , Dijkman R , Hoffmann D , Thiel V , Beer M , Benarafa C . Nature 2021 602 (7896) 307-313 Emerging variants of concern (VOC) drive the SARS-CoV-2 pandemic(1,2). Experimental assessment of replication and transmission of major VOC compared to progenitors are needed to understand successful emerging mechanisms of VOC(3). Here, we show that Alpha and Beta spike (S) proteins have a greater affinity to human angiotensin converting enzyme 2 (hACE2) receptor over the progenitor variant (wt-S(614G)) in vitro. Yet Alpha and wt-S(614G) had similar replication kinetics in human nasal airway epithelial cultures, whereas Beta was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over the progenitor variant (wt-S(614G)) in ferrets and two mouse models, where the substitutions in S were major drivers for fitness advantage. In hamsters, supporting high replication levels, Alpha and wt-S(614G) had comparable fitness. In contrast, Beta was outcompeted by Alpha and wt-S(614G) in hamsters and hACE2-expressing mice. Our study highlights the importance of using multiple models for complete fitness characterization of VOC and demonstrates adaptation of Alpha towards increased upper respiratory tract replication and enhanced transmission in vivo in restrictive models, whereas Beta fails to overcome contemporary strains in naïve animals. |
N-glycosylation profiles of the SARS-CoV-2 spike D614G mutant and its ancestral protein characterized by advanced mass spectrometry.
Wang D , Zhou B , Keppel TR , Solano M , Baudys J , Goldstein J , Finn MG , Fan X , Chapman AP , Bundy JL , Woolfitt AR , Osman SH , Pirkle JL , Wentworth DE , Barr JR . Sci Rep 2021 11 (1) 23561 N-glycosylation plays an important role in the structure and function of membrane and secreted proteins. The spike protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is heavily glycosylated and the major target for developing vaccines, therapeutic drugs and diagnostic tests. The first major SARS-CoV-2 variant carries a D614G substitution in the spike (S-D614G) that has been associated with altered conformation, enhanced ACE2 binding, and increased infectivity and transmission. In this report, we used mass spectrometry techniques to characterize and compare the N-glycosylation of the wild type (S-614D) or variant (S-614G) SARS-CoV-2 spike glycoproteins prepared under identical conditions. The data showed that half of the N-glycosylation sequons changed their distribution of glycans in the S-614G variant. The S-614G variant showed a decrease in the relative abundance of complex-type glycans (up to 45%) and an increase in oligomannose glycans (up to 33%) on all altered sequons. These changes led to a reduction in the overall complexity of the total N-glycosylation profile. All the glycosylation sites with altered patterns were in the spike head while the glycosylation of three sites in the stalk remained unchanged between S-614G and S-614D proteins. |
Effects of indoor air movement and ambient temperature on mosquito (Anopheles gambiae) behaviour around bed nets: implications for malaria prevention initiatives
Sutcliffe JF , Yin S . Malar J 2021 20 (1) 427 BACKGROUND: Until recently, relatively little research has been done on how mosquitoes behave around the occupied bed net in the indoor environment. This has been partly remedied in the last few years through laboratory and field studies, most of these using video methods and mosquito flight tracking. Despite these recent advances, understanding of the mosquito-bed net environment system, and the principles that underlie mosquito behaviour within it, is limited. This project aimed to further understand this system by studying the effects of gently moving air (such as might be introduced through room design to make the indoor environment more comfortable and conducive to ITN use) and warmer vs. cooler ambient conditions on mosquito activity around ITNs and other bed nets. METHODS: The activity of colonized female Anopheles gambiae around an occupied untreated bed net set up in a mosquito-proof tent in a large laboratory space was recorded under different ambient conditions using a laser detection-video recording system. Conditions tested were 'cool' (23-25 °C) and 'warm' (27-30 °C) air temperatures and the presence or absence of a cross-flow produced by a small central processing unit (CPU) fan pointed at the side of the net so that it produced a 'low-' or 'high-' speed cross-draught (approx. 0.1 and 0.4 m/s, respectively). Near-net activity in recordings was measured using video image analysis. RESULTS: In cool, still air conditions, more than 80% of near-net activity by An. gambiae occurred on the net roof. Introduction of the low-speed or high-speed cross-draught resulted in an almost total drop off in roof activity within 1 to 2 min and, in the case of the high-speed cross-draught, a complementary increase in activity on the net side. In warm, still conditions, near-net activity appeared to be lower overall than in cool, still air conditions and to be relatively less focussed on the roof. Introduction of the high-speed cross-draught in warm conditions resulted in a decrease in roof activity and increase in side activity though neither effect was statistically significant. CONCLUSIONS: Results are interpreted in terms of the flow of the stimulatory odour plume produced by the net occupant which, consistent with established principles of fluid dynamics, appears to rise quickly and remain more intact above the net occupant in cool, still air than in warm, still air. Cross-draught effects are ascribed to the changes they cause in the flow of the host odour plume as opposed to mosquito flight directly. The implications of these results for house designs that promote indoor air movement, on bed net design, and on other vector control measures are discussed. How mosquitoes approach a net is influenced both by indoor temperature and ventilation and their interaction. This system is in need of further study. |
Susceptibility to SARS-CoV-2 of Cell Lines and Substrates Commonly Used to Diagnose and Isolate Influenza and Other Viruses.
Wang L , Fan X , Bonenfant G , Cui D , Hossain J , Jiang N , Larson G , Currier M , Liddell J , Wilson M , Tamin A , Harcourt J , Ciomperlik-Patton J , Pang H , Dybdahl-Sissoko N , Campagnoli R , Shi PY , Barnes J , Thornburg NJ , Wentworth DE , Zhou B . Emerg Infect Dis 2021 27 (5) 1380-1392 Co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses has been reported. We evaluated cell lines commonly used to isolate viruses and diagnose related diseases for their susceptibility to SARS-CoV-2. Although multiple kidney cell lines from monkeys were susceptible to SARS-CoV-2, we found many cell types derived from humans, dogs, minks, cats, mice, and chicken were not. We analyzed MDCK cells, which are most commonly used for surveillance and study of influenza viruses, and found that they were not susceptible to SARS-CoV-2. The low expression level of the angiotensin converting enzyme 2 receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by overexpression of canine angiotensin converting enzyme 2 in trans, strengthened the cellular barrier to productive infection. Moreover, a D614G mutation in the spike protein did not appear to affect SARS-CoV-2 cell tropism. Our findings should help avert inadvertent propagation of SARS-CoV-2 from diagnostic cell lines. |
Use of the prostate-specific antigen (PSA) test in the United States for men age 65, 1999-2015: Implications for practice interventions
Shahangian S , Fan L , Sharma KP , Siegel DA . Cancer Rep (Hoboken) 2021 4 (4) e1352 BACKGROUND: Various professional organizations have issued recommendations on use of the PSA test to screen for prostate cancer in different age groups. AIMS: Using Medicare claims databases, we aimed to determine rates of PSA testing in the context of screening recommendations during 1999-2015 for US men age ≥65, stratified by age group and census regions, after excluding claims relating to all prostate-related conditions. METHODS AND RESULTS: Medicare claims databases encompassed 9.71-11.12 million men for the years under study. PSA testing rate was the proportion of men with ≥1 test(s) per 12 months of continuous enrollment. Men diagnosed with any prostate-related condition were excluded. Annual percent change (APC) in PSA test use was estimated using joinpoint regression analysis. In 1999-2015, annual testing rate was 10.1%-23.1%, age ≥85; 16.6%-31.0%, age 80-84; 23.8%-35.8%, age 75-79; 28.3%-36.9%, age 70-74; and 26.4%-33.6%, age 65-69. From 1999 to 2015, PSA testing rate decreased 40.7%, 29.9%, 13.9%, and 2.9%, respectively, for men age ≥85, 80-84, 75-79, and 70-74. For men age 65-69, test use increased by 0.3%. Significant APC trends were: APC(1999-2002) = +8.1%, P = .029 and APC(2008-2015) = -9.0%, P < .001 for men age ≥85; APC(2008-2015) = -7.1%, P = .001 for men age 80-84; APC(2001-2015) = -2.5%, P < .001 for men age 75-79; APC(2008-2015) = -3.3%, P = .007 for men age 70-74; and APC(2010-2015) = -5.2%, P = .014 for men age 65-69. COCLUSION: Although decreased from 1999 to 2015, PSA testing rates remained high for men age ≥70. Further research could help understand why PSA testing continues inconsistent with recommendations. |
Use of the prostate-specific antigen test in the U.S. for men age 30 to 64 in 2011 to 2017 using a large commercial claims database: Implications for practice interventions
Shahangian S , Sharma KP , Fan L , Siegel DA . Cancer Rep (Hoboken) 2021 4 (4) e1365 BACKGROUND: Given the public health relevance of PSA-based screening, various professional organizations have issued recommendations on the use of the PSA test to screen for prostate cancer in different age groups. AIM: Using a large commercial claims database, we aimed to determine the most recent rates of PSA testing for privately insured men age 30 to 64 in the context of screening recommendations. METHODS AND RESULTS: Data from employer plans were from MarketScan commercial claims database. Annual PSA testing rate was the proportion of men with ≥1 paid test(s) per 12 months of continuous enrollment. Men with diagnosis of any prostate-related condition were excluded. Annual percent change (APC) in PSA test use was estimated using joinpoint regression analysis. In 2011 to 2017, annual testing rate encompassing 5.02 to 5.53 million men was approximately 1.4%, age 30 to 34; 3.4% to 4.1%, age 35 to 39; 11% to 13%, age 40 to 44; 18% to 21%, age 45 to 49; 31% to 33%, age 50 to 54; 35% to 37%, age 55 to 59; and 38% to 41%, age 60 to 64. APC for 2011 to 2017 was -0.5% (P = .11), age 30 to 34; -3.0% (P = .001), age 35-39; -3.1% (P < .001), age 40 to 44; -2.4% (P = .001), age 45 to 49; -0.2% (P = .66), age 50 to 54; 0.0% (P = .997), age 55 to 59; and -3.3% (P = .054) from 2011 to 2013 and 1.2% (P = .045) from 2013 to 2017, age 60 to 64. PSA testing rate decreased from 2011 to 2017 for age groups between 35 and 49 by 13.4% to 16.9%. CONCLUSIONS: Based on these data, PSA testing rate has modestly decreased from 2011 to 2017. These results, however, should be considered in view of the limitation that MarketScan claims data may not be equated to actual PSA testing practices in the entire U.S. population age 30 to 64. Future research should be directed to understand why clinicians continue ordering PSA test for men younger than 50. |
SARS-CoV-2 spike D614G change enhances replication and transmission.
Zhou B , Thi Nhu Thao T , Hoffmann D , Taddeo A , Ebert N , Labroussaa F , Pohlmann A , King J , Steiner S , Kelly JN , Portmann J , Halwe NJ , Ulrich L , Trüeb BS , Fan X , Hoffmann B , Wang L , Thomann L , Lin X , Stalder H , Pozzi B , de Brot S , Jiang N , Cui D , Hossain J , Wilson M , Keller M , Stark TJ , Barnes JR , Dijkman R , Jores J , Benarafa C , Wentworth DE , Thiel V , Beer M . Nature 2021 592 (7852) 122-127 During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic(1). However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human host cell surface receptor angiotensin-converting enzyme 2 (ACE2), (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro, it provides a real competitive advantage in vivo, particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating. |
Assessing the burden of congenital rubella syndrome in China and evaluating mitigation strategies: a metapopulation modelling study
Su Q , Feng Z , Hao L , Ma C , Hagan JE , Grant GB , Wen N , Fan C , Yang H , Rodewald LE , Wang H , Glasser JW . Lancet Infect Dis 2021 21 (7) 1004-1013 BACKGROUND: A rubella vaccine was licensed in China in 1993 and added to the Expanded Programme on Immunization in 2008, but a national cross-sectional serological survey during 2014 indicates that many adolescents remain susceptible. Maternal infections during the first trimester often cause miscarriages, stillbirths, and, among livebirths, congenital rubella syndrome. We aimed to evaluate possible supplemental immunisation activities (SIAs) to accelerate elimination of rubella and congenital rubella syndrome. METHODS: We analysed residual samples from the national serological survey done in 2014, data from monthly rubella surveillance reports from 2005 and 2016, and additional publications through a systematic review. Using an age-structured population model with provincial strata, we calculated the reproduction numbers and evaluated the gradient of the metapopulation effective reproduction number with respect to potential supplemental immunisation rates. We corroborated these analytical results and estimated times-to-elimination by simulating SIAs among adolescents (ages 10-19 years) and young adults (ages 20-29 years) using a model with regional strata. We estimated the incidence of rubella and burden of congenital rubella syndrome by simulating transmission in a relatively small population lacking only spatial structure. FINDINGS: By 2014, childhood immunisation had reduced rubella's reproduction number from 7·6 to 1·2 and SIAs among adolescents were the optimal elimination strategy. We found that less than 10% of rubella infections were reported; that although some women with symptomatic first-trimester infections might have elected to terminate their pregnancies, 700 children could have been born with congenital rubella syndrome during 2014; and that timely SIAs would avert outbreaks that, as susceptible adolescents reached reproductive age, could greatly increase the burden of this syndrome. INTERPRETATION: Our findings suggest that SIAs among adolescents would most effectively reduce congenital rubella syndrome as well as eliminate rubella, owing both to fewer infections in the immunised population and absence of infections that those immunised would otherwise have caused. Metapopulation models with realistic mixing are uniquely capable of assessing such indirect effects. FUNDING: WHO and National Science Foundation. |
Metagenomic sequencing generates the whole genomes of porcine rotavirus A, C, and H from the United States.
Hull JJA , Qi M , Montmayeur AM , Kumar D , Velasquez DE , Moon SS , Magaña LC , Betrapally N , Ng TFF , Jiang B , Marthaler D . PLoS One 2020 15 (12) e0244498 The genus Rotavirus comprises eight species, designated A to H, and two recently identified tentative species I in dogs and J in bats. Species Rotavirus A, B, C and H (RVA, RVB, RVC and RVH) have been detected in humans and animals. While human and animal RVA are well characterized and defined, complete porcine genome sequences in the GenBank are limited compared to human strains. Here, we used a metagenomic approach to sequence the 11 segments of RVA, RVC and RVH strains from piglets in the United States (US) and explore the evolutionary relations of these RV species. Metagenomics identified Astroviridae, Picornaviridae, Caliciviridae, Coronoviridae in samples MN9.65 and OK5.68 while Picobirnaviridae and Arteriviridae were only identified in sample OK5.68. Whole genome sequencing and phylogenetic analyses identified multiple genotypes with the RVA of strain MN9.65 and OK5.68, with the genome constellation of G5/G9-P[7]/P[13]-I5/I5- R1/R1-C1-M1-A8-N1-T7-E1/E1-H1 and G5/G9-P[6]/P[7]-I5-R1/R1-C1-M1-A8-N1-T1/T7-E1/E1-H1, respectively. The RVA strains had a complex evolutionary relationship with other mammalian strains. The RVC strain OK5.68 had a genome constellation of G9-P[6]-I1-R1-C5-M6-A5-N1-T1-E1-H1, and shared an evolutionary relationship with porcine strains from the US. The RVH strains MN9.65 and OK5.68 had the genome constellation of G5-P1-I1-R1-C1-M1-A5-N1-T1-E4-H1 and G5-P1-I1-R1-C1-M1-A5-N1-T1-E1-H1, indicating multiple RVH genome constellations are circulating in the US. These findings allow us to understand the complexity of the enteric virome, develop improved screening methods for RVC and RVH strains, facilitate expanded rotavirus surveillance in pigs, and increase our understanding of the origin and evolution of rotavirus species. |
Sleep disturbances and disability following work-related injury and illness: Examining longitudinal relationships across three follow-up waves
Fan JK , Sim M , Lilley R , Wong IS , Smith PM . J Sleep Res 2020 30 (3) e13124 Despite the high burden of sleep disturbances among the general population, there is limited information on prevalence and impact of poor sleep among injured workers. This study: (a) estimated the prevalence of sleep disturbance following work-related injury; and (b) examined the longitudinal association between sleep disturbances and disability/functioning, accounting for reciprocal relationships and mental illness. Longitudinal survey data were collected from workers' compensation claimants with a time-loss claim in Victoria, Australia (N = 700). Surveys were conducted at baseline, 6 months and 12 months. Sleep disturbance was measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire. Disability/functioning was based on self-reported activity limitations, participation restrictions and emotional functioning. Path models examined the association between disability/functioning and sleep. Mean sleep disturbance T-scores were 55.2 (SD 11.4) at 6 months, with 36.4% of the sample having a T-score of 60+. Longitudinal relationships were observed between disability (specifically, emotional functioning) and sleep disturbances across successive follow-up waves. For example, each unit increase in T2 emotional functioning (five-point scale) was associated with a 1.1 unit increase in T3 sleep disturbance (approximately 29-76 scale). Cross-lagged path models found evidence of a reciprocal relationship between disability and sleep, although adjustment for mental illness attenuated the estimates to the null. In conclusion, sleep disturbances are common among workers' compensation claimants with work injuries/illnesses. Given the links between some dimensions of disability, mental health and sleep disturbances, the findings have implications for the development of interventions that target the high prevalence of sleep problems among working populations. |
Provision of Pediatric Immunization Services During the COVID-19 Pandemic: an Assessment of Capacity Among Pediatric Immunization Providers Participating in the Vaccines for Children Program - United States, May 2020.
Vogt TM , Zhang F , Banks M , Black C , Arthur B , Kang Y , Lucas P , Lamont B . MMWR Morb Mortal Wkly Rep 2020 69 (27) 859-863 Recent reports suggest that routine childhood immunization coverage might have decreased during the coronavirus disease 2019 (COVID-19) pandemic (1,2). To assess the capacity of pediatric health care practices to provide immunization services to children during the pandemic, a survey of practices participating in the Vaccines for Children (VFC) program was conducted during May 12-20, 2020. Data were weighted to account for the sampling design; thus, all percentages reported are weighted. Among 1,933 responding practices, 1,727 (89.8%) were currently open; 1,397 (81.1%) of these reported offering immunization services to all of their patients. When asked whether the practice would likely be able to accommodate new patients to assist with provision of immunization services through August, 1,135 (59.1%) respondents answered affirmatively. These results suggest that health care providers appear to have the capacity to deliver routinely recommended childhood vaccines, allowing children to catch up on vaccines that might have been delayed as a result of COVID-19-related effects on the provision of or demand for routine well child care. Health care providers and immunization programs should educate parents on the need to return for well-child and immunization visits or refer patients to other practices, if they are unable to provide services (3). |
The effect of variant interference on de novo assembly for viral deep sequencing.
Castro CJ , Marine RL , Ramos E , Ng TFF . BMC Genomics 2020 21 (1) 421 BACKGROUND: Viruses have high mutation rates and generally exist as a mixture of variants in biological samples. Next-generation sequencing (NGS) approaches have surpassed Sanger for generating long viral sequences, yet how variants affect NGS de novo assembly remains largely unexplored. RESULTS: Our results from > 15,000 simulated experiments showed that presence of variants can turn an assembly of one genome into tens to thousands of contigs. This "variant interference" (VI) is highly consistent and reproducible by ten commonly-used de novo assemblers, and occurs over a range of genome length, read length, and GC content. The main driver of VI is pairwise identities between viral variants. These findings were further supported by in silico simulations, where selective removal of minor variant reads from clinical datasets allow the "rescue" of full viral genomes from fragmented contigs. CONCLUSIONS: These results call for careful interpretation of contigs and contig numbers from de novo assembly in viral deep sequencing. |
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