Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 1237 Records) |
Query Trace: Chen A[original query] |
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An updated framework for SARS-CoV-2 variants reflects the unpredictability of viral evolution
Subissi L , Otieno JR , Worp N , Attar Cohen H , Oude Munnink BB , Abu-Raddad LJ , Alm E , Barakat A , Barclay WS , Bhiman JN , Caly L , Chand M , Chen M , Cullinane A , de Oliveira T , Drosten C , Druce J , Effler P , El Masry I , Faye A , Ghedin E , Grant R , Haagmans BL , Happi C , Herring BL , Hodcroft EB , Ikejezie J , Katawera V , Kassamali ZA , Leo YS , Leung GM , Kondor RJ , Marklewitz M , Mendez-Rico J , Melhem NM , Munster V , Nahapetyan K , Naindoo D , Oh DY , Peacock TP , Peiris M , Peng Z , Poon LLM , Rambaut A , Saha S , Shen Y , Siqueira MM , Volz E , Tessema SK , Thiel V , Triki H , van der Werf S , von Eije K , Cunningham J , Koopmans MPG , von Gottberg A , Agrawal A , Van Kerkhove MD . Nat Med 2024 |
Biomarkers of organophosphate and polybrominated diphenyl ether (PBDE) flame retardants of American workers and associations with inhalation and dermal exposures
Estill CF , Mayer AC , Chen IC , Slone J , LaGuardia MJ , Jayatilaka N , Ospina M , Sjodin A , Calafat AM . Environ Sci Technol 2024 This study evaluated workers' exposures to flame retardants, including polybrominated diphenyl ethers (PBDEs), organophosphate esters (OPEs), and other brominated flame retardants (BFRs), in various industries. The study aimed to characterize OPE metabolite urinary concentrations and PBDE serum concentrations among workers from different industries, compare these concentrations between industries and the general population, and evaluate the likely route of exposure (dermal or inhalation). The results showed that workers from chemical manufacturing had significantly higher (p <0.05) urinary concentrations of OPE metabolites compared to other industries. Spray polyurethane foam workers had significantly higher (p <0.05) urinary concentrations of bis(1-chloro-2-propyl) phosphate (BCPP) compared to other industries. Electronic scrap workers had higher serum concentrations of certain PBDE congeners compared to the general population. Correlations were observed between hand wipe samples and air samples containing specific flame-retardant parent chemicals and urinary metabolite concentrations for some industries, suggesting both dermal absorption and inhalation as primary routes of exposure for OPEs. Overall, this study provides insights into occupational exposure to flame retardants in different industries and highlights the need for further research on emerging flame retardants and exposure reduction interventions. |
Challenges of COVID-19 case forecasting in the US, 2020-2021
Lopez VK , Cramer EY , Pagano R , Drake JM , O'Dea EB , Adee M , Ayer T , Chhatwal J , Dalgic OO , Ladd MA , Linas BP , Mueller PP , Xiao J , Bracher J , Castro Rivadeneira AJ , Gerding A , Gneiting T , Huang Y , Jayawardena D , Kanji AH , Le K , Mühlemann A , Niemi J , Ray EL , Stark A , Wang Y , Wattanachit N , Zorn MW , Pei S , Shaman J , Yamana TK , Tarasewicz SR , Wilson DJ , Baccam S , Gurung H , Stage S , Suchoski B , Gao L , Gu Z , Kim M , Li X , Wang G , Wang L , Wang Y , Yu S , Gardner L , Jindal S , Marshall M , Nixon K , Dent J , Hill AL , Kaminsky J , Lee EC , Lemaitre JC , Lessler J , Smith CP , Truelove S , Kinsey M , Mullany LC , Rainwater-Lovett K , Shin L , Tallaksen K , Wilson S , Karlen D , Castro L , Fairchild G , Michaud I , Osthus D , Bian J , Cao W , Gao Z , Lavista Ferres J , Li C , Liu TY , Xie X , Zhang S , Zheng S , Chinazzi M , Davis JT , Mu K , Pastore YPiontti A , Vespignani A , Xiong X , Walraven R , Chen J , Gu Q , Wang L , Xu P , Zhang W , Zou D , Gibson GC , Sheldon D , Srivastava A , Adiga A , Hurt B , Kaur G , Lewis B , Marathe M , Peddireddy AS , Porebski P , Venkatramanan S , Wang L , Prasad PV , Walker JW , Webber AE , Slayton RB , Biggerstaff M , Reich NG , Johansson MA . PLoS Comput Biol 2024 20 (5) e1011200 During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making. |
Gestational PBDE concentrations, persistent externalizing, and emerging internalizing behaviors in adolescents: The HOME study
Cecil KM , Xu Y , Chen A , Khoury J , Altaye M , Braun JM , Sjodin A , Lanphear BP , Newman N , Strawn JR , Vuong AM , Yolton K . Environ Res 2024 252 118981 BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental chemicals used as flame retardants in commercial and consumer products. Gestational PBDE concentrations are associated with adverse behaviors in children; however, the persistence of these associations into adolescence remains understudied. OBJECTIVE: We estimated the association of gestational PBDE serum concentrations with early adolescent self- and caregiver-reported behaviors at age 12 years and determined the consistency with previously observed associations in childhood with caregiver-reported behaviors in a prospective pregnancy and birth cohort. METHODS: We measured maternal serum concentrations of five individual PBDE congeners and created a summary exposure variable (∑(5)BDE: 28, -47, -99, -100 and -153) during pregnancy. At age 12 years, we assessed behaviors for 237 adolescents using self- and caregiver-reports with the Behavioral Assessment System for Children-3 (BASC3). We used multivariable linear regression models to estimate covariate-adjusted associations of lipid standardized, log(10)-transformed gestational PBDE concentrations with BASC3 scores. We obtained estimates and 95% confidence intervals through a bootstrapping approach. We evaluated potential effect measure modification (EMM) of adolescent sex by examining sex-stratified regression models and estimating the EMM p-values. RESULTS: Gestational PBDE concentrations were positively associated with adolescent-reported BASC3 composite indices for inattention & hyperactivity (BDE-28, -47, -99, -100, ∑(5)BDE), internalizing problems (BDE-28, -47, -99), functional impairment (BDE-28, ∑(5)BDE), and emotional symptoms (BDE-28). Gestational PBDE concentrations were positively associated with caregiver-reported BASC3 composite indices for externalizing problems (BDE-28, -47, -99, -100, -153, ∑(5)BDE) and behavioral symptoms (BDE-99). For caregiver reported behaviors, we observed stronger associations with gestational BDE concentrations among males, especially for executive functioning (BDE-28, -47, -99, -100, ∑(5)BDE). DISCUSSION: Gestational PBDE serum concentrations were associated with self-reported internalizing and externalizing behavior problems in early adolescence. Caregiver-reported externalizing behaviors recognized during childhood remain associated with gestational PBDE concentrations and persist into early adolescence. Internalizing behaviors were less recognized by caregivers. |
Descriptive epidemiology of pathogens associated with acute respiratory infection in a community-based study of K-12 school children (2015-2023)
Bell C , Goss M , Norton D , Barlow S , Temte E , He C , Hamer C , Walters S , Sabry A , Johnson K , Chen G , Uzicanin A , Temte J . Pathogens 2024 13 (4) School-based outbreaks often precede increased incidence of acute respiratory infections in the greater community. We conducted acute respiratory infection surveillance among children to elucidate commonly detected pathogens in school settings and their unique characteristics and epidemiological patterns. The ORegon CHild Absenteeism due to Respiratory Disease Study (ORCHARDS) is a longitudinal, laboratory-supported, school-based, acute respiratory illness (ARI) surveillance study designed to evaluate the utility of cause-specific student absenteeism monitoring for early detection of increased activity of influenza and other respiratory viruses in schools from kindergarten through 12th grade. Eligible participants with ARIs provided demographic, epidemiologic, and symptom data, along with a nasal swab or oropharyngeal specimen. Multipathogen testing using reverse-transcription polymerase chain reaction (RT-PCR) was performed on all specimens for 18 respiratory viruses and 2 atypical bacterial pathogens (Chlamydia pneumoniae and Mycoplasma pneumoniae). Between 5 January 2015 and 9 June 2023, 3498 children participated. Pathogens were detected in 2455 of 3498 (70%) specimens. Rhinovirus/enteroviruses (36%) and influenza viruses A/B (35%) were most commonly identified in positive specimens. Rhinovirus/enteroviruses and parainfluenza viruses occurred early in the academic year, followed by seasonal coronaviruses, RSV, influenza viruses A/B, and human metapneumovirus. Since its emergence in 2020, SARS-CoV-2 was detected year-round and had a higher median age than the other pathogens. A better understanding of the etiologies, presentations, and patterns of pediatric acute respiratory infections can help inform medical and public health system responses. |
Prevalence, patterns, and predictors of SARS-CoV-2 RNA and culturable virus in tears of case-ascertained household cohort
So M , Goldberg SA , Lu S , Garcia-Knight M , Davidson MC , Tassetto M , Murray VW , Anglin K , Pineda-Ramirez J , Chen JY , Rugart PR , Richardson ET , Hagen MB , Midgley CM , Andino R , Seitzman GD , Gonzales J , Peluso MJ , Martin JN , Kelly JD . Am J Ophthalmol 2024 PURPOSE: To investigate the prevalence, patterns, and predictors of SARS-CoV-2 RNA and culturable virus in tears of case-ascertained household cohort. DESIGN: Prospective, longitudinal case-ascertained household cohort identified through convenience sampling. METHODS: This analysis was restricted to individuals who were non-hospitalized, symptomatic, and tested positive for SARS-CoV-2 by nasal RT-PCR. Tears and anterior nasal biospecimens were serially collected throughout the acute period. Tears specimens were collected by the study staff using Schirmer test strips, and nasal specimens were self-collected. For both, SARS-CoV-2 RNA was quantified using qRT-PCR and culturable virus was detected using presence of cytopathic effect (CPE) in tissue culture; positive CPE was confirmed by a qRT-PCR step. A series of cross-sectional unadjusted analyses were performed investigating the relationship between different sociodemographic determinants and biological factors associated with tears RNA positivity. RESULTS: Among the 83 SARS-CoV-2 infected participants, ten (12%) had at least one RNA positive tears specimen. Amongst these ten, five (50%) had concurrent presence of culturable virus, at a median of 7 days post symptom onset (IQR: 4-7 days) (absolute range: 4-8 days). CONCLUSIONS: In this longitudinal cohort, we found evidence of culturable virus in the tears of a small proportion of non-hospitalized SARS-CoV-2 infected individuals. Current public health infection precautions do not account for transmission via tears, so these findings may improve our understanding of potential sources of SARS-CoV-2 transmission and contribute to developing future guidelines. |
Biodynamic modeling and analysis of human-exoskeleton interactions during assisted manual handling
Chen Y , Yin W , Zheng L , Mehta R , Zhang X . Proc Hum Factors Ergon Soc 2023 67 803-806 The objective of this study was to investigate the effects of a back exoskeleton on joint kinematics and kinetics during assisted manual handling tasks using subject-specific musculoskeletal biodynamic models and model-based analyses. We constructed these musculoskeletal models using OpenSim (Delp et al., 2007), incorporating optical motion capture, ground reaction forces (GRFs) measurements, and humanexoskeleton interactive force input. Our long-term goal is to enable digital modeling and simulation that can aid in the design and development of more effective exoskeletons and safer manual handling practices. © 2023 Human Factors and Ergonomics Society. |
Predictors of corporal punishment during the COVID-19 pandemic
Sege RD , Purdue EL , Burstein D , Holditch Niolon P , Price LL , Chen Y , Swedo EA , Piazza Hurley T , Prasad K , Klika B . Pediatr Rep 2024 16 (2) 300-312 Although current policies discourage the use of corporal punishment (CP), its use is still widespread in the US. The objective of this study was to assess the proportion of parents who used CP during the pandemic and identify related risk and protective factors. We analyzed results of a nationwide cross-sectional internet panel survey of 9000 US caregivers who responded in three waves from November 2020 to July 2021. One in six respondents reported having spanked their child in the past week. Spanking was associated with intimate partner violence and the use of multiple discipline strategies and not significantly associated with region or racial self-identification. Parents who spanked sought out more kinds of support, suggesting an opportunity to reduce spanking through more effective parenting resources. Additionally, these results suggest that parents who report using CP may be at risk for concurrent domestic violence. |
Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease
Hoenigl M , Arastehfar A , Arendrup MC , Brüggemann R , Carvalho A , Chiller T , Chen S , Egger M , Feys S , Gangneux JP , Gold JAW , Groll AH , Heylen J , Jenks JD , Krause R , Lagrou K , Lamoth F , Prattes J , Sedik S , Wauters J , Wiederhold NP , Thompson GR 3rd . Clin Microbiol Rev 2024 e0007423 SUMMARYFungal infections are on the rise, driven by a growing population at risk and climate change. Currently available antifungals include only five classes, and their utility and efficacy in antifungal treatment are limited by one or more of innate or acquired resistance in some fungi, poor penetration into "sequestered" sites, and agent-specific side effect which require frequent patient reassessment and monitoring. Agents with novel mechanisms, favorable pharmacokinetic (PK) profiles including good oral bioavailability, and fungicidal mechanism(s) are urgently needed. Here, we provide a comprehensive review of novel antifungal agents, with both improved known mechanisms of actions and new antifungal classes, currently in clinical development for treating invasive yeast, mold (filamentous fungi), Pneumocystis jirovecii infections, and dimorphic fungi (endemic mycoses). We further focus on inhaled antifungals and the role of immunotherapy in tackling fungal infections, and the specific PK/pharmacodynamic profiles, tissue distributions as well as drug-drug interactions of novel antifungals. Finally, we review antifungal resistance mechanisms, the role of use of antifungal pesticides in agriculture as drivers of drug resistance, and detail detection methods for antifungal resistance. |
Time-varying associations of gestational and childhood triclosan with pubertal and adrenarchal outcomes in early adolescence
Laue HE , Lanphear BP , Calafat AM , Cecil KM , Chen A , Xu Y , Kalkwarf HJ , Madan JC , Karagas MR , Yolton K , Fleisch AF , Braun JM . Environ Epidemiol 2024 8 (2) e305 BACKGROUND: Triclosan is an endocrine-disrupting chemical, but associations with pubertal outcomes remain unclear. We examined associations of gestational and childhood triclosan with adolescent hormone concentrations and pubertal stage. METHODS: We quantified urinary triclosan concentrations twice during pregnancy and seven times between birth and 12 years in participants recruited from Cincinnati, OH (2003-2006). We averaged concentrations across pregnancy and childhood and separately considered individual exposure periods in multiple informant models. At 12 years, we measured serum hormone concentrations (males [n = 72] and females [n = 84]-dehydroepiandrosterone-sulfate, luteinizing hormone, follicle-stimulating hormone; males-testosterone; females-estradiol). Also at age 12 years, participants self-reported physical development and menarchal timing. We estimated associations (95% confidence interval) of triclosan with hormone concentrations, more advanced physical development, and age at menarche. RESULTS: For females, each doubling of childhood triclosan was associated with 16% lower estradiol concentrations (-29%, 0%), with stronger associations for measures closer to adolescence. We found suggestive evidence that higher triclosan at any age was associated with ~10% (for gestational triclosan: -18%, -2%) lower follicle-stimulating hormone concentrations among males and early postnatal (1-3 years) triclosan was associated with 63% (5%, 96%) lower odds of advanced pubic hair development in females. In multiple informant models, each doubling of gestational triclosan concentrations was associated with 5% (0%, 9%) earlier age at menarche, equivalent to 5.5 months. CONCLUSION: Gestational and childhood triclosan concentrations were related to some pubertal outcomes including hormone concentrations and age at menarche. Our findings highlight the relevance of elucidating potential sex-specific and time-dependent actions of triclosan. |
Predicting state level suicide fatalities in the United States with realtime data and machine learning
Patel D , Sumner SA , Bowen D , Zwald M , Yard E , Wang J , Law R , Holland K , Nguyen T , Mower G , Chen Y , Johnson JI , Jespersen M , Mytty E , Lee JM , Bauer M , Caine E , De Choudhury M . Npj Ment Health Res 2024 3 (1) 3 Digital trace data and machine learning techniques are increasingly being adopted to predict suicide-related outcomes at the individual level; however, there is also considerable public health need for timely data about suicide trends at the population level. Although significant geographic variation in suicide rates exist by state within the United States, national systems for reporting state suicide trends typically lag by one or more years. We developed and validated a deep learning based approach to utilize real-time, state-level online (Mental Health America web-based depression screenings; Google and YouTube Search Trends), social media (Twitter), and health administrative data (National Syndromic Surveillance Program emergency department visits) to estimate weekly suicide counts in four participating states. Specifically, per state, we built a long short-term memory (LSTM) neural network model to combine signals from the real-time data sources and compared predicted values of suicide deaths from our model to observed values in the same state. Our LSTM model produced accurate estimates of state-specific suicide rates in all four states (percentage error in suicide rate of -2.768% for Utah, -2.823% for Louisiana, -3.449% for New York, and -5.323% for Colorado). Furthermore, our deep learning based approach outperformed current gold-standard baseline autoregressive models that use historical death data alone. We demonstrate an approach to incorporate signals from multiple proxy real-time data sources that can potentially provide more timely estimates of suicide trends at the state level. Timely suicide data at the state level has the potential to improve suicide prevention planning and response tailored to the needs of specific geographic communities. |
Neutralization of rubella vaccine virus and immunodeficiency-related vaccine-derived rubella viruses by intravenous immunoglobulins
Chen MH , Perelygina L , Hao L , Beard RS , Lackner C , Farcet MR , Karbiener M , Icenogle J , Kreil TR . J Infect Dis 2024 The association between granulomas and vaccine-derived rubella virus (VDRV) in people with primary immune deficiencies (PID) has raised concerns about the ability of immunoglobulin (IG) preparations to neutralize VDRVs. We investigated the capacity of IG to neutralize rubella vaccine virus and four VDRV strains. As expected, the rubella vaccine virus itself was potently neutralized by IG preparations; however, the VDRV isolates from patients after intra-host evolution, 2-6 times less so. Diagnosis of immune deficiencies before possible live-virus vaccination is thus of critical importance, while IG replacement therapy can be expected to provide protection from rubella virus infection. | The occurrence of granulomas associated with vaccine derived rubella viruses (VDRV) in people with primary immune deficiencies (PID) challenges immunoglobulin (IG) preparations regarding their rubella neutralizing ability. This study confirmed potent rubella virus neutralization capacity of IG preparations and thus suggests protection of IG-treated PID patients against rubella. The study also highlights the importance of early diagnosis and timely given IG to prevent possible systemic spread of VDRV persisting locally in granulomas. | eng |
SARS-CoV-2 infection, inflammation and birth outcomes in a prospective NYC pregnancy cohort
Gigase FAJ , Jessel RH , Kaplowitz E , Boychuk N , Ohrn S , Ibroci Est , Castro J , Lynch J , Tubassum R , Balbierz A , Molenaar NM , Graziani M , Missall R , Flores T , Stern T , Carreno JM , Krammer F , Adler A , Brody RI , Lesseur C , Chen J , Ellington S , Galang RR , Snead MC , Howell E , Stone J , Bergink V , Dolan S , Lieb W , Rommel AS , de Witte LD , Janevic T . J Reprod Immunol 2024 163 104243 Associations between antenatal SARS-CoV-2 infection and pregnancy outcomes have been conflicting and the role of the immune system is currently unclear. This prospective cohort study investigated the interaction of antenatal SARS-CoV-2 infection, changes in cytokine and HS-CRP levels, birthweight and gestational age at birth. 2352 pregnant participants from New York City (2020-2022) were included. Plasma levels of interleukin (IL)-1β, IL-6, IL-17A and high-sensitivity C-reactive protein (HS-CRP) were quantified in blood specimens obtained across pregnancy. Quantile and linear regression models were conducted to 1) assess the impact of antenatal SARS-CoV-2 infection, overall and by timing of detection of SARS-CoV-2 positivity (< 20 weeks versus ≥ 20 weeks), on birthweight and gestational age at delivery; 2) examine the relationship between SARS-CoV-2 infection and maternal immune changes during pregnancy. All models were adjusted for maternal demographic and obstetric factors and pandemic timing. Birthweight models were additionally adjusted for gestational age at delivery and fetal sex. Immune marker models were also adjusted for gestational age at specimen collection and multiplex assay batch. 371 (15.8%) participants were infected with SARS-CoV-2 during pregnancy, of which 98 (26.4%) were infected at < 20 weeks gestation. Neither SARS-CoV-2 infection in general nor in early or late pregnancy was associated with lower birthweight nor earlier gestational age at delivery. Further, we did not observe cytokine or HS-CRP changes in response to SARS-CoV-2 infection and thus found no evidence to support a potential association between immune dysregulation and the diversity in pregnancy outcomes following infection. |
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. |
Heterogeneity in measures of illness among patients with myalgic encephalomyelitis/chronic fatigue syndrome is not explained by clinical practice: A study in seven U.S. Specialty clinics
Unger ER , Lin JMS , Chen Y , Cornelius ME , Helton B , Issa AN , Bertolli J , Klimas NG , Balbin EG , Bateman L , Lapp CW , Springs W , Podell RN , Fitzpatrick T , Peterson DL , Gottschalk CG , Natelson BH , Blate M , Kogelnik AM , Phan CC . J Clin Med 2024 13 (5) Background: One of the goals of the Multi-site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM) study was to evaluate whether clinicians experienced in diagnosing and caring for patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) recognized the same clinical entity. Methods: We enrolled participants from seven specialty clinics in the United States. We used baseline data (n = 465) on standardized questions measuring general clinical characteristics, functional impairment, post-exertional malaise, fatigue, sleep, neurocognitive/autonomic symptoms, pain, and other symptoms to evaluate whether patient characteristics differed by clinic. Results: We found few statistically significant and no clinically significant differences between clinics in their patients’ standardized measures of ME/CFS symptoms and function. Strikingly, patients in each clinic sample and overall showed a wide distribution in all scores and measures. Conclusions: Illness heterogeneity may be an inherent feature of ME/CFS. Presenting research data in scatter plots or histograms will help clarify the challenge. Relying on case–control study designs without subgrouping or stratification of ME/CFS illness characteristics may limit the reproducibility of research findings and could obscure underlying mechanisms. © 2024 by the authors. |
A teenage girl with altered mental status and paraparesis
Miyakawa R , Louie J , Keh C , Chen L , Javid B , Ernst JD , Goswami N , Chow FC . J Clin Tuberc Other Mycobact Dis 2024 35 100425 A teenage girl presented with fever and altered mental status. MRI showed diffuse leptomeningeal enhancement of the brain and spine. She was diagnosed by a positive cerebrospinal fluid (CSF) culture with tuberculous (TB) meningitis and was started on anti-TB medications and corticosteroids. Her mental status improved, but she was noted to have proximal weakness of the lower extremities. In the course of tapering corticosteroids at week 11 of anti-TB therapy, she became acutely confused and febrile. MRI demonstrated interval development of tuberculomas in the brain and a mass lesion in the thoracic spine causing cord compression. Given the clinical picture was suggestive of a paradoxical reaction, the dose of corticosteroids was increased. Infliximab was added when repeat MRI revealed enlargement of the mass lesion in the spine with worsening cord compression. She was successfully tapered off of corticosteroids. Over several months, the patient's motor function recovered fully, and she returned to ambulating without assistance. |
Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel
Lester SN , Stumpf M , Freeman BD , Mills L , Schiffer J , Semenova V , Jia T , Desai R , Browning P , Alston B , Ategbole M , Bolcen S , Chen A , David E , Manitis P , Tatum H , Qin Y , Zellner B , Drobeniuc J , Tejada-Strop A , Chatterjee P , Shrivastava-Ranjan P , Jenks MH , McMullan LK , Flint M , Spiropoulou CF , Niemeyer GP , Werner BJ , Bean CJ , Johnson JA , Hoffmaster AR , Satheshkumar PS , Schuh AJ , Owen SM , Thornburg NJ . Access Microbiol 2024 6 (2) Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of rRT-PCR confirmed COVID-19 patients' sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4-96.6 %. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698 to 0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies. |
Dietary and physical activity behaviors among high school students - Youth Risk Behavior Survey, United States, 2019
Merlo CL , Jones SE , Michael SL , Chen TJ , Sliwa SA , Lee SH , Brener ND , Lee SM , Park S . MMWR Suppl 2020 69 (1) 64-76 Establishing healthy dietary and physical activity patterns among youths is an important public health strategy for improving health and preventing chronic diseases; however, few adolescents meet U.S. government recommendations for dietary or physical activity behaviors, and disparities by sex and race/ethnicity exist. CDC analyzed data from the 2019 Youth Risk Behavior Survey to update estimates of dietary and physical activity behaviors among U.S. high school students overall and by sex and race/ethnicity. In addition, 2-year comparisons (2017 and 2019) and trends in prevalence of these behaviors during 2009-2019 were examined. In 2019, overall, during the 7 days before the survey, 41.8% of students had eaten fruit or drunk 100% fruit juices <1 time/day; 40.7% had eaten vegetables <1 time/day; and 16.7% had not eaten breakfast on all 7 days. Moreover, although 57.4% of students had played on ≥1 sports team during the 12 months before the survey, less than half of students had been physically active for ≥60 minutes/day on all 7 days (23.2%), had exercised to strengthen or tone their muscles on ≥3 days/week (49.5%), had met both aerobic and muscle-strengthening physical activity guidelines (16.5%), or had attended physical education classes on all 5 days in an average school week (25.9%). Trend data indicate limited progress in shifting dietary and physical activity behaviors. That is, with the exception of decreases in the percentage of students who had consumed soda ≥1 time/day (2009: 29.2%; 2019: 15.1%), sports drinks ≥1 time/day (2015: 13.8%; 2019: 10.6%), and <3 glasses/day of plain water (2015: 50.5%; 2019: 44.6%), high school students' dietary and physical activity behaviors have not improved and, in certain cases, have worsened. These findings support the need for multicomponent approaches, including policy and environmental changes, and opportunities for adolescents to learn about and practice making healthy choices. |
Dietary and physical activity behaviors in 2021 and changes from 2019 to 2021 among high school students - Youth Risk Behavior Survey, United States, 2021
Michael SL , Jones SE , Merlo CL , Sliwa SA , Lee SM , Cornett K , Brener ND , Chen TJ , Ashley CL , Park S . MMWR Suppl 2023 72 (1) 75-83 The fall of 2021 was the first school semester to begin with widespread in-person learning since the COVID-19 pandemic began. Understanding dietary and physical activity behaviors of adolescents during this time can provide insight into potential health equity gaps and programmatic needs in schools and communities. This report uses data from the 2021 national Youth Risk Behavior Survey conducted among a nationally representative sample of U.S. public and private school students in grades 9-12 to update estimates of dietary and physical activity behaviors among U.S. high school students overall and by sex and race and ethnicity. In addition, 2-year comparisons (2019 versus 2021) of these behaviors were examined. In 2021, daily consumption of fruits, vegetables, and breakfast during the past 7 days remained low and decreased overall with specific disparities by sex and race and ethnicity from 2019 to 2021. The overall prevalence of students attending physical education classes daily, exercising to strengthen muscles on ≥3 days/week (i.e., met the guideline for muscle-strengthening activity), and playing on at least one sports team decreased from 2019 to 2021; whereas being physically active for ≥60 minutes/day on all 7 days (i.e., met the guideline for aerobic activity) and meeting both aerobic and muscle-strengthening guidelines remained low but did not change. These findings underscore the need for strategies to increase healthy dietary and physical activity behaviors both in the recovery phase of COVID-19 and longer term. |
Expansion of Neisseria meningitidis serogroup C clonal complex 10217 during meningitis outbreak, Burkina Faso, 2019
Kekeisen-Chen JF , Tarbangdo FT , Sharma S , Marasini D , Marjuki H , Kibler JL , Reese HE , Ouattara S , Ake FH , Yameogo I , Ouedraogo I , Seini E , Zoma RL , Tonde I , Sanou M , Novak RT , McNamara LA . Emerg Infect Dis 2024 30 (3) 460-468 During January 28-May 5, 2019, a meningitis outbreak caused by Neisseria meningitidis serogroup C (NmC) occurred in Burkina Faso. Demographic and laboratory data for meningitis cases were collected through national case-based surveillance. Cerebrospinal fluid was collected and tested by culture and real-time PCR. Among 301 suspected cases reported in 6 districts, N. meningitidis was the primary pathogen detected; 103 cases were serogroup C and 13 were serogroup X. Whole-genome sequencing revealed that 18 cerebrospinal fluid specimens tested positive for NmC sequence type (ST) 10217 within clonal complex 10217, an ST responsible for large epidemics in Niger and Nigeria. Expansion of NmC ST10217 into Burkina Faso, continued NmC outbreaks in the meningitis belt of Africa since 2019, and ongoing circulation of N. meningitidis serogroup X in the region underscore the urgent need to use multivalent conjugate vaccines in regional mass vaccination campaigns to reduce further spread of those serogroups. |
Correction: Testing and treatment for malaria elimination: a systematic review
Newby G , Cotter C , Roh ME , Harvard K , Bennett A , Hwang J , Chitnis N , Fine S , Stresman G , Chen I , Gosling R , Hsiang MS . Malar J 2024 23 (1) 63 |
Long noncoding RNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote lung carcinogenesis
Wang PS , Liu Z , Sweef O , Xie J , Chen J , Zhu H , Zeidler-Erdely PC , Yang C , Wang Z . Environ Int 2024 185 108494 Hexavalent chromium [Cr(VI)] is a common environmental pollutant and chronic exposure to Cr(VI) causes lung cancer in humans, however, the mechanism of Cr(VI) carcinogenesis has not been well understood. Lung cancer is the leading cause of cancer-related death, although the mechanisms of how lung cancer develops and progresses have been poorly understood. While long non-coding RNAs (lncRNAs) are found abnormally expressed in cancer, how dysregulated lncRNAs contribute to carcinogenesis remains largely unknown. The goal of this study is to investigate the mechanism of Cr(VI)-induced lung carcinogenesis focusing on the role of the lncRNA ABHD11 antisense RNA 1 (tail to tail) (ABHD11-AS1). It was found that the lncRNA ABHD11-AS1 expression levels are up-regulated in chronic Cr(VI) exposure-transformed human bronchial epithelial cells, chronically Cr(VI)-exposed mouse lung tissues, and human lung cancer cells as well. Bioinformatics analysis revealed that ABHD11-AS1 levels are up-regulated in lung adenocarcinomas (LUADs) tissues and associated with worse overall survival of LUAD patients but not in lung squamous cell carcinomas. It was further determined that up-regulation of ABHD11-AS1 expression plays an important role in chronic Cr(VI) exposure-induced cell malignant transformation and tumorigenesis, and the stemness of human lung cancer cells. Mechanistically, it was found that ABHD11-AS1 directly binds SART3 (spliceosome associated factor 3, U4/U6 recycling protein). The interaction of ABHD11-AS1 with SART3 promotes USP15 (ubiquitin specific peptidase 15) nuclear localization. Nuclear localized USP15 interacts with pre-mRNA processing factor 19 (PRPF19) to increase CD44 RNA alternative splicing activating β-catenin and enhancing cancer stemness. Together, these findings indicate that lncRNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote cell malignant transformation and lung carcinogenesis. |
Association of contact sexual violence victimization and health in the U.S.
Basile KC , Chen J , Friar NW , Smith SG , Leemis R . Am J Prev Med 2024 INTRODUCTION: Sexual violence victimization is related to negative impacts, including chronic health conditions. Less is known about possible confounders of this relationship. This study examines the association between lifetime experience of contact sexual violence (CSV) and health conditions by sex, controlling for demographics and other victimization. METHODS: Data are from the 2016/2017 National Intimate Partner and Sexual Violence Survey, a nationally representative study of English- or Spanish-speaking adults. Ten health conditions (e.g., HIV/AIDS) and four activity limitations (e.g., difficulty dressing) were examined related to CSV victimization. Logistic regression models examined the association between CSV victimization and health controlling for demographics and other victimization experiences. Analyses were conducted in 2022-2023. RESULTS: For women and men, many health conditions and activity limitations were significantly associated with CSV after controlling for demographics. Accounting for other victimization, female CSV victims had higher odds of experiencing difficulty sleeping (Adjusted Odds Ratio [AOR]=1.3); difficulty concentrating, remembering, or making decisions (AOR=1.7); and difficulty doing errands alone (AOR=1.4) than non-victims. Male victims had higher odds than non-victims of having HIV/AIDS (AOR=5.2); frequent headaches (AOR=1.5); chronic pain (AOR=1.5); difficulty sleeping (AOR=1.4); serious difficulty hearing (AOR=1.3); and difficulty concentrating, remembering, or making decisions (AOR=1.5). CONCLUSIONS: CSV had a negative impact on health, although other types of victimization appear to also have an impact, especially for women. Demographic characteristics also aid the understanding of the relationship between CSV and health. Efforts to prevent CSV and other forms of violence can be coupled with healthcare- and population-level approaches to improve long-term health. |
Global distribution of Leptospira serovar isolations and detections from animal host species: A systematic review and online database
Hagedoorn NN , Maze MJ , Carugati M , Cash-Goldwasser S , Allan KJ , Chen K , Cossic B , Demeter E , Gallagher S , German R , Galloway RL , Habuš J , Rubach MP , Shiokawa K , Sulikhan N , Crump JA . Trop Med Int Health 2024 OBJECTIVES: Leptospira, the spirochaete causing leptospirosis, can be classified into >250 antigenically distinct serovars. Although knowledge of the animal host species and geographic distribution of Leptospira serovars is critical to understand the human and animal epidemiology of leptospirosis, current data are fragmented. We aimed to systematically review, the literature on animal host species and geographic distribution of Leptospira serovars to examine associations between serovars with animal host species and regions and to identify geographic regions in need of study. METHODS: Nine library databases were searched from inception through 9 March 2023 using keywords including Leptospira, animal, and a list of serovars. We sought reports of detection of Leptospira, from any animal, characterised by cross agglutinin absorption test, monoclonal antibody typing, serum factor analysis, or pulsed-field gel electrophoresis to identify the serovar. RESULTS: We included 409 reports, published from 1927 through 2022, yielding data on 154 Leptospira serovars. The reports included data from 66 (26.5%) of 249 countries. Detections were from 144 animal host species including 135 (93.8%) from the class Mammalia, 5 (3.5%) from Amphibia, 3 (2.1%) from Reptilia, and 1 (0.7%) from Arachnida. Across the animal host species, Leptospira serovars that were detected in the largest number of animal species included Grippotyphosa (n = 39), Icterohaemorrhagiae (n = 29), Pomona (n = 28), Australis (n = 25), and Ballum (n = 25). Of serovars, 76 were detected in a single animal host species. We created an online database to identify animal host species for each serovar by country. CONCLUSIONS: We found that many countries have few or no Leptospira serovars detected from animal host species and that many serovars were detected from a single animal species. Our study highlights the importance of efforts to identify animal host species of leptospirosis, especially in places with a high incidence of human leptospirosis. We provide an updated resource for leptospirosis researchers. |
Implementing a continuous quality-improvement framework for tuberculosis infection prevention and control in healthcare facilities in China, 2017-2019
Zhang C , O'Connor S , Smith-Jeffcoat SE , Rodriguez DF , Guo H , Hao L , Chen H , Sun Y , Li Y , Xu J , Chen L , Xia L , Yang X , Date A , Cheng J . Infect Control Hosp Epidemiol 2024 1-7 BACKGROUND: Tuberculosis (TB) infection prevention and control (IPC) in healthcare facilities is key to reducing transmission risk. A framework for systematically improving TB IPC through training and mentorship was implemented in 9 healthcare facilities in China from 2017 to 2019. METHODS: Facilities conducted standardized TB IPC assessments at baseline and quarterly thereafter for 18 months. Facility-based performance was assessed using quantifiable indicators for IPC core components and administrative, environmental, and respiratory protection controls, and as a composite of all control types We calculated the percentage changes in scores over time and differences by IPC control type and facility characteristics. RESULTS: Scores for IPC core components increased by 72% during follow-up when averaged across facilities. The percentage changes for administrative, environmental, and respiratory protection controls were 39%, 46%, and 30%, respectively. Composite scores were 45% higher after the intervention. Overall, scores increased most during the first 6 months. There was no association between IPC implementation and provincial economic development or volume of TB services. CONCLUSIONS: TB IPC policies and practices showed most improvement early during implementation and did not differ consistently by facility characteristics. The training component of the project helped increase the capacity of healthcare professionals to manage TB transmission risks. Lessons learned here will inform national TB IPC guidance. |
The association between state minimum wage and firearm homicides, 2000-2020
Merrill-Francis M , Chen MS , Dunphy C , Lennon NH , Grady C , Miller GF , McCourt AD . Am J Prev Med 2024 INTRODUCTION: Recent research has indicated an association between both poverty and income inequality and firearm homicides. Increased minimum wages may serve as a strategy for reducing firearm violence by increasing economic security among workers earning low wages and reducing the number of families living in poverty. This study aimed to examine the association between state minimum wage and firearm homicides in the United States between 2000 and 2020. METHODS: State minimum wage, obtained from Temple's Law Atlas and augmented by legal research, was conceptualized using the Kaitz Index. State-level homicide counts were obtained from 2000-2020 multiple-cause-of death mortality data from the National Vital Statistics System. Log-linear regressions were conducted to model the associations between state minimum wage and firearm homicides, stratifying by demographic groups. Analyses were conducted in 2023. RESULTS: A one percentage point increase in a state's Kaitz Index was associated with a 1.3% (95% CI: -2.1% to -0.5%) decrease in a state's firearm homicide rate. When interacted with quartile of firearm ownership, the Kaitz Index was associated with decreases in firearm homicide in all except the lowest quartile. These findings were largely consistent across stratifications. CONCLUSIONS: Changing a state's minimum wage, whereby a full-time minimum wage worker's salary is closer to a state's median income may be an option for reducing firearm homicides. |
Molecular and Phenotypic Characterization of a Highly Evolved Type 2 Vaccine-Derived Poliovirus Isolated from Seawater in Brazil, 2014.
Cassemiro KM , Burlandy FM , Barbosa MR , Chen Q , Jorba J , Hachich EM , Sato MI , Burns CC , da Silva EE . PLoS One 2016 11 (3) e0152251 A type 2 vaccine-derived poliovirus (VDPV), differing from the Sabin 2 strain at 8.6% (78/903) of VP1 nucleotide positions, was isolated from seawater collected from a seaport in São Paulo State, Brazil. The P1/capsid region is related to the Sabin 2 strain, but sequences within the 5'-untranslated region and downstream of the P1 region were derived from recombination with other members of Human Enterovirus Species C (HEV-C). The two known attenuating mutations had reverted to wild-type (A481G in the 5'-UTR and Ile143Thr in VP1). The VDPV isolate had lost the temperature sensitive phenotype and had accumulated amino acid substitutions in neutralizing antigenic (NAg) sites 3a and 3b. The date of the initiating OPV dose, estimated from the number of synonymous substitutions in the capsid region, was approximately 8.5 years before seawater sampling, a finding consistent with a long time of virus replication and possible transmission among several individuals. Although no closely related type 2 VDPVs were detected in Brazil or elsewhere, this VDPV was found in an area with a mobile population, where conditions may favor both viral infection and spread. Environmental surveillance serves as an important tool for sensitive and early detection of circulating poliovirus in the final stages of global polio eradication. |
Epidemiologic and genetic characteristics of mumps viruses isolated in China from 1995 to 2010.
Cui A , Zhu Z , Chen M , Zheng H , Liu L , Wang Y , Ma Y , Wang C , Fang X , Li P , Guan R , Wang S , Zhou J , Zheng L , Gao H , Ding Z , Li L , Bo F , Sun Z , Zhang Z , Feng D , He J , Chen H , Jin L , Rota PA , Xu W . Infect Genet Evol 2014 21 384-90 The epidemiologic and genetic characteristics of mumps viruses detected in China from 1995 to 2010 were analyzed in this study. Mumps remains endemic in China with a high overall incidence rate. The incidence of mumps in Western China was higher than that in other regions of the country. Each year, most of mumps cases occurred between April and July, but a small peak also occurred in November and December. Mumps cases primarily affected the under 15 year old age group. Virologic data demonstrated that genotype F was the predominant circulating genotype throughout China for at least 15 years and no other genotype was detected between 1995 and 2010. Analysis of sequence data from the small hydrophobic (SH) gene indicated that multiple transmission chains of genotype F were found in various provinces of China, with no apparent chronologic and geographic restriction. This is the first report describing the epidemiology of mumps and genetic characterization of mumps viruses at the national level in China. |
The third international hackathon for applying insights into large-scale genomic composition to use cases in a wide range of organisms.
Walker K , Kalra D , Lowdon R , Chen G , Molik D , Soto DC , Dabbaghie F , Khleifat AA , Mahmoud M , Paulin LF , Raza MS , Pfeifer SP , Agustinho DP , Aliyev E , Avdeyev P , Barrozo ER , Behera S , Billingsley K , Chong LC , Choubey D , De Coster W , Fu Y , Gener AR , Hefferon T , Henke DM , Höps W , Illarionova A , Jochum MD , Jose M , Kesharwani RK , Kolora SRR , Kubica J , Lakra P , Lattimer D , Liew CS , Lo BW , Lo C , Lötter A , Majidian S , Mendem SK , Mondal R , Ohmiya H , Parvin N , Peralta C , Poon CL , Prabhakaran R , Saitou M , Sammi A , Sanio P , Sapoval N , Syed N , Treangen T , Wang G , Xu T , Yang J , Zhang S , Zhou W , Sedlazeck FJ , Busby B . F1000Res 2022 11 530 In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics. |
Large-scale validation of skin prion seeding activity as a biomarker for diagnosis of prion diseases
Zhang W , Orrú CD , Foutz A , Ding M , Yuan J , Shah SZA , Zhang J , Kotobelli K , Gerasimenko M , Gilliland T , Chen W , Tang M , Cohen M , Safar J , Xu B , Hong DJ , Cui L , Hughson AG , Schonberger LB , Tatsuoka C , Chen SG , Greenlee JJ , Wang Z , Appleby BS , Caughey B , Zou WQ . Acta Neuropathol 2024 147 (1) 17 Definitive diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) relies on the examination of brain tissues for the pathological prion protein (PrP(Sc)). Our previous study revealed that PrP(Sc)-seeding activity (PrP(Sc)-SA) is detectable in skin of sCJD patients by an ultrasensitive PrP(Sc) seed amplification assay (PrP(Sc)-SAA) known as real-time quaking-induced conversion (RT-QuIC). A total of 875 skin samples were collected from 2 cohorts (1 and 2) at autopsy from 2-3 body areas of 339 cases with neuropathologically confirmed prion diseases and non-sCJD controls. The skin samples were analyzed for PrP(Sc)-SA by RT-QuIC assay. The results were compared with demographic information, clinical manifestations, cerebrospinal fluid (CSF) PrP(Sc)-SA, other laboratory tests, subtypes of prion diseases defined by the methionine (M) or valine (V) polymorphism at residue 129 of PrP, PrP(Sc) types (#1 or #2), and gene mutations in deceased patients. RT-QuIC assays of the cohort #1 by two independent laboratories gave 87.3% or 91.3% sensitivity and 94.7% or 100% specificity, respectively. The cohort #2 showed sensitivity of 89.4% and specificity of 95.5%. RT-QuIC of CSF available from 212 cases gave 89.7% sensitivity and 94.1% specificity. The sensitivity of skin RT-QuIC was subtype dependent, being highest in sCJDVV1-2 subtype, followed by VV2, MV1-2, MV1, MV2, MM1, MM1-2, MM2, and VV1. The skin area next to the ear gave highest sensitivity, followed by lower back and apex of the head. Although no difference in brain PrP(Sc)-SA was detected between the cases with false negative and true positive skin RT-QuIC results, the disease duration was significantly longer with the false negatives [12.0 ± 13.3 (months, SD) vs. 6.5 ± 6.4, p < 0.001]. Our study validates skin PrP(Sc)-SA as a biomarker for the detection of prion diseases, which is influenced by the PrP(Sc) types, PRNP 129 polymorphisms, dermatome sampled, and disease duration. |
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