bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 Antibody Prevalence and Association with Routine Laboratory Values in a Life Insurance Applicant Population
Authors: Rigatti Steven J. , Stout Robert 
Published: September 2020

AbstractObjectivesThe prevalence of SARS-CoV-2 antibodies in the general population is largely unknown. Since many infections, even among the elderly and other vulnerable populations, are asymptomatic, the prevalence of antibodies could help determine how far along the path to herd immunity the general population has progressed. Also, in order to clarify the clinical manifestations of current or recent past COVID-19 illness, it may be useful to determine if there are any common alterations in routine clinical laboratory values.MethodsWe performed SARS-CoV-2 antibody tests on 50,130 consecutive life insurance applicants who were having blood drawn for the purpose of underwriting (life risk assessment). Subjects were also tested for lipids, liver function tests, renal function studies, as well as serum proteins. Other variables included height, weight, blood pressure at the time of the blood draw, and history of common chronic diseases (hypertension, heart disease, diabetes, and cancer).ResultsThe overall prevalence of SARS-CoV-2 was 3.0%, and was fairly consistent across the age range and similar in males and females. Several of the routine laboratory tests obtained were significantly different in antibody-positive vs. antibody-negative subjects, including albumin, globulins, bilirubin, and the urine albumin:creatinine ratio. The BMI was also significantly higher in the antibody-positive group. Geographical distribution revealed a very high level of positivity in the state of New York compared to all other areas (17.1%). Using state population data from the US Census, it is estimated that this level of seropositivity would correspond to 6.98 million (99% CI: 6.56-7.38 million) SARS-CoV-2 infections in the US, which is 3.8 times the cumulative number of cases in the US reported to the CDC as of June 1, 2020.ConclusionsThe estimated number of total SARS-CoV-2 infections based on positive serology is substantially higher than the total number of cases reported to the CDC. Certain laboratory values, particularly serum protein levels, are associated with positive serology, though these associations are not likely to be clinically meaningful.
TGF-β1 in extracellular vesicles from HIV-infected plasma and macrophages linked to cardiopulmonary dysfunction
Authors: Krishnamachary Balaji , Agarwal Stuti , Mahajan Aatish , Kumar Ashok , Mohan Aradhana , Chen Ling , Hsue Priscilla , Chalise Prabhakar , Morris Alison , Dhillon Navneet K. 
Published: September 2020

AbstractRationaleExtracellular vesicles (EVs) have emerged as important mediators in cell-cell communication and disease pathogenesis; however, their relevance in pulmonary hypertension (PH) secondary to HIV infection is yet to be explored.ObjectiveTo examine the role of circulating small EVs and monocyte-derived macrophage (MDM) EVs in the development of HIV-associated PHMethodsEVs isolated from plasma of HIV-infected drug users and non-users with/without PH and from supernatants of HIV-infected MDMs treated with/without second hit of cocaine were studied for their effect on vascular dysfunction both in vitro and in vivo.Measurements and Main ResultsWe report significantly higher numbers of plasma derived EVs (PEVs) carrying higher levels of TGF-β1 in people living with HIV (PLWH) that had PH compared to non-PH PLWH. Importantly, levels of these TGF-β1 loaded PEVs correlated with pulmonary arterial systolic pressures, CD4 counts, but not with diffusion capacity for carbon monoxide or viral load. Correspondingly, enhanced TGF-β1-dependent pulmonary endothelial injury and smooth muscle hyperplasia was observed. Cocaine treatment of HIV-1 infected-MDMs resulted in increased number of TGF-β1 high-EVs. Intravenous injection of these EVs in rats led to increased right ventricle systolic pressure accompanied with myocardial injury and increased levels of serum endothelin-1, TNF-α, and cardiac Troponin-I. Conversely, pretreatment of rats with TGFβ-Receptor 1 inhibitor prevented these EV-mediated changes.ConclusionFindings define the ability of macrophage-derived small EVs to cause pulmonary vascular modeling and PH via modulation of TGF-β signaling and suggest clinical implications of circulating TGF-β high-EVs as a potential biomarker of HIV-PH.
COVID-19Predict – Predicting Pandemic Trends
Authors: Bosch Jürgen , Wilson Austin , O’Neil Karthik , Zimmerman Peter A. 
Published: September 2020

AbstractBackgroundGiven the global public health importance of the COVID-19 pandemic, data comparisons that predict on-going infection and mortality trends across national, state and county-level administrative jurisdictions are vitally important. We have designed a COVID-19 dashboard with the goal of providing concise sets of summarized data presentations to simplify interpretation of basic statistics and location-specific current and short-term future risks of infection.MethodsWe perform continuous collection and analyses of publicly available data accessible through the COVID-19 dashboard hosted at Johns Hopkins University (JHU github). Additionally, we utilize the accumulation of cases and deaths to provide dynamic 7-day short-term predictions on these outcomes across these national, state and county administrative levels.FindingsCOVID-19Predict produces 2,100 daily predictions [or calculations] on the state level (50 States x3 models x7 days x2 cases and deaths) and 131,964 (3,142 Counties x3 models x7 days x2 cases and deaths) on the county level. To assess how robust our models have performed in making short-term predictions over the course of the pandemic, we used available case data for all 50 U.S. states spanning the period January 20 - August 16 2020 in a retrospective analysis. Results showed a 3.7% to −0.2% mean error of deviation from the actual case predictions to date.InterpretationOur transparent methods and admin-level visualizations provide real-time data reporting and forecasts related to on-going COVID-19 transmission allowing viewers (individuals, health care providers, public health practitioners and policy makers) to develop their own perspectives and expectations regarding public life activity decisions.FundingFinancial resources for this study have been provided by Case Western Reserve University.
A Co-infection model for HPV and Syphilis with Optimal Control and Cost-Effectiveness Analysis
Authors: Omame A. , Okuonghae D. , Nwafor U. E. , Odionyenma B. U. 
Published: September 2020

AbstractIn this work, we develop and present a co-infection model for human papillomavirus (HPV) and syphilis with cost-effectiveness optimal control analysis. The full co-infection model is shown to undergo the phenomenon of backward bifurcation when a certain condition is satisfied. The global asymptotic stability of the disease-free equilibrium of the full model is shown not to exist, when the associated reproduction number is less than unity. The existence of endemic equilibrium of the syphilis-only sub-model is shown to exist and the global asymptotic stability of the disease-free and endemic equilibria of both the syphilis-only sub-model and HPV-only sub-model were established. The global asymptotic stability of disease-free equilibrium of the HPV-only sub-model is also proven. Numerical simulations of the optimal control model showed that the optimal control strategy which implements syphilis treatment controls for singly infected individuals is the most cost-effective of all the control strategies in reducing the burden of HPV and syphilis co-infections.
Oxygen Saturation or breathlessness? – how best to predict pneumonia in patients presenting with a cough to primary care
Authors: Chambers Elspeth , Stuart Beth , Moore Michael , Lown Mark 
Published: September 2020

SYNOPSISBackgroundDistinguishing pneumonia from acute bronchitis has an important bearing on treatment decisions. The best validated diagnostic decision rule was derived from the GRACE-09 study. The 3Cs study provides oxygen saturations in addition to clinical signs and symptoms. Oxygen saturation is a predictor in hospital settings and may be beneficial in primary care.ObjectivesThis project evaluates whether the data from GRACE-09 and 3Cs studies can be mapped onto each other and be combined dataset to refine the diagnostic accuracy of the GRACE-09 clinical prediction rule for the diagnosis of pneumonia.Patients and MethodsGRACE-09 included 3106 patients with acute cough in a multicentre European study. 3Cs is a UK based study of 28883 patients with acute cough.Binary logistic regression was used in the 3Cs dataset to determine which variables significantly predicted low oxygen saturation (<95%). Statistically significant predictors were determined using area under curve (AUC). This equation was used to model the probability of low oxygen saturation in the GRACE-09 dataset and subsequently included in the GRACE-09 model to determine whether low oxygen saturation is a comparable predictor to breathlessness in predicting pneumonia.ResultsFor 3Cs, using all seven variables achieved an AUC for low oxygen saturation of 0.73 (95% CI 0.72-0.74). Substituting low oxygen saturation into GRACE-09 model gives AUC 0.75 (95% CI 0.69-0.82) compared to original GRACE-09 using breathlessness and gives AUC 0.77 (95% CI 0.73-0.82).ConclusionsLow oxygen saturation and breathlessness are similarly predictive and could be used interchangeably in a modified GRACE-09 prediction model.KEY MESSAGESCan pulse oximetry replace subjective breathlessness assessment in the GRACE-09 prediction rule? Pulse oximetry gives an objective measurement that can be used to assist the diagnosis of pneumonia in primary care.
Influence of Malaria Edemicity and Standardized TB Prevalence to BCG Coverage on Covid-19 Mortality
Authors: Raham Tareef Fadhil 
Published: September 2020

AbstractBackgroundRegarding SARS-CoV-2 it is well known that a substantial percentage of adult population cannot get infected if exposed to this novel coronavirus. Several studies give primary indication of the possible role of preexisting immunity whether cross immunity or not. Possible role of latent TB and BCG and malaria have been already suggested to create innate cross heterogeneous immunity. We look for influence of these factors on Covid-19 mortality in malarious countries.Material and methods80 malarious countries are enrolled in this study. Hierarchical multiple regression type of analyses is used for data analyses. TB prevalence/ 100,000 population standardized to BCG coverage rates is taken as direct factor in the test. Malaria incidence /1000 population is considered as intermediate factor and the outcome is COVID-19 mortality/ 1 million (M) population.ResultsTB prevalence is associated with reduced COVID-19 mortality and malaria have an additional effect in reducing COVID-19 mortality. The results show with robust statistical support that TB prevalence was also associated with reduced COVID-19 mortality with additional effect that is also observed in TB and BCG coverage rate.ConclusionsMalaria and standardized TB prevalence are statistical significant factors predicting COVID-19 mortality in negative associations.
Daytime variation in SARS-CoV-2 infection and cytokine production
Authors: Diallo Aïssatou Bailo , Gay Laetitia , Coiffard Benjamin , Leone Marc , Mezouar Soraya , Mege Jean-Louis 
Published: September 2020

AbstractS. Ray and A. Reddy recently anticipated the implication of circadian rhythm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of the coronavirus disease (Covid-19). In addition to its key role in the regulation of biological functions, the circadian rhythm has been suggested as a regulator of viral infections. Specifically, the time of day of infection was found critical for illness progression, as has been reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. We analyzed circadian rhythm implication in SARS-CoV-2 virus infection of isolated human monocytes, key actor cells in Covid-19 disease, from healthy subjects. The circadian gene expression ofBmal1andClockgenes was investigated with q-RTPCR. Monocytes were infected with SARS-CoV-2 virus strain and viral infection was investigated by One-Step qRT-PCR and immunofluorescence. Interleukin (IL)-6, IL-1β and IL-10 levels were also measured in supernatants of infected monocytes. Using Cosinor analysis, we showed thatBmal1andClocktranscripts exhibited circadian rhythm in monocytes with an acrophase and a bathyphase at Zeitgeber Time (ZT)6 and ZT17. After forty-eight hours, the amount of SARS-CoV-2 virus increased in the monocyte infected at ZT6 compared to ZT17. The high virus amount at ZT6 was associated with significant increased release in IL-6, IL-1β and IL-10 compared to ZT17. Our results suggest that time day of SARS-CoV-2 infection affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease progression and we propose circadian rhythm as a novel target for managing viral progression.ImportanceThe implication of circadian rhythm (CR) in pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been recently anticipated. The time of day of infection is critical for illness progression as reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. In this study, we wondered if SARS-CoV-2 infection and cytokine production by human monocytes, innate immune cells affected by Covid-19, were regulated by CR. Our results suggest that time day of SARS-CoV-2 infection affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease progression and we propose circadian rhythm as a novel target for managing viral progression.
Variants inPRKAR1Bcause a neurodevelopmental disorder with autism spectrum disorder,apraxia, and insensitivity to pain
Authors: Marbach Felix , Stoyanov Georgi , Erger Florian , Rosenfeld Jill A. , Torti Erin , Haldeman-Englert Chad , Sklirou Evgenia , Kessler Elena , Ceulemans Sophia , Nelson Stanley F. , Martinez-Agosto Julian A. , Palmer Christina G.S. , Signer Rebecca H. ,   Undiagnosed Diseases Network, Andrews Marisa V. , Grange Dorothy K. , Willaert Rebecca , Person Richard , Telegrafi Aida , Lichtarge Olivier , Katsonis Panagiotis , Stocco Amber , Schaaf Christian P. 
Published: September 2020

AbstractPurposeWe characterize the phenotypes of six unrelated individuals with intellectual disability and autism spectrum disorder, who carry heterozygous missense-variants of thePRKAR1Bgene.MethodsVariants ofPRKAR1Bwere identified by single-exome or trio-exome analysis. We contacted the families and physicians of the six individuals in order to collect clinical and phenotypic information.ResultsPRKAR1Bencodes the R1β subunit of the cyclic AMP-dependent protein kinase A (PKA), and is predominantly expressed in the central nervous system. Recent studies of patient cohorts with neurodevelopmental disorders found significant enrichment ofde novomissense variants inPRKAR1B, andin vivostudies of the murine ortholog demonstrated altered hippocampal function and reduced neurogenic inflammation and long-term nociceptive pain in R1β-deficient mice.In our study,de novoorigin of thePRKAR1B-variants could be confirmed in five out of six individuals, and four carried the same heterozygousde novovariant c.1003C>T (p. Arg335Trp; NM_001164760). Global developmental delay, autism spectrum disorder, and apraxia/dyspraxia has been reported in all six, and reduced pain sensitivity was found in three individuals carrying the c.1003C>T variant.ConclusionOur study provides strong evidence for a novel,PRKAR1B-related neurodevelopmental disorder.
COVID-19: Mechanistic model calibration subject to active and varying non-pharmaceutical interventions
Authors: Willis Mark J. , Wright Allen , Bramfitt Victoria , Díaz Victor Hugo Grisales 
Published: September 2020

AbstractMathematical models are useful in epidemiology to understand the COVID-19 contagion dynamics. Our aim is to demonstrate the effectiveness of parameter regression methods to calibrate an established epidemiological model describing COVID-19 infection rates subject to active and varying non-pharmaceutical interventions (NPIs). To do this, we assess the potential of some established chemical engineering modelling principles and practice for application to modelling of epidemiological systems. This allows us to exploit the sophisticated functionality of a commercial chemical engineering simulator capable of parameter regression with piecewise continuous integration and event and discontinuity management. Our results provide insights into the outcomes of on-going disease suppression measures, while visualisation of reported data also provides up-to-date condition monitoring of the status of the pandemic. We observe that the effective reproduction number response to NPIs is non-linear with variable response rate, magnitude and direction.HighlightsModelling COVID-19 contagion dynamics with piecewise continuous integration and event and discontinuity managementEquivalence to kinetic model with time varying stoichiometryModel calibration and estimation of non-linear variation in ReDevelopment of prototype demonstrator algorithm for estimation of Re using data with time varying NPIs
Bacterial pulmonary superinfections are associated with unfavourable outcomes in critically ill COVID-19 patients
Authors: Buehler Philipp K. , Zinkernagel Annelies S. , Hofmaenner Daniel A. , García Pedro David Wendel , Acevedo Claudio T. , Gómez-Mejia Alejandro , Shambat Srikanth Mairpady , Andreoni Federica , Maibach Martina A. , Bartussek Jan , Hilty Matthias P. , Frey Pascal M. , Schuepbach Reto A. , Brugger Silvio D. 
Published: September 2020

AbstractObjectivesWhile superinfections are associated with unfavourable disease course, their impact on clinical outcomes in critically ill COVID-19 patients remains largely unknown. We aimed to investigate the burden of superinfections in COVID-19 patients.MethodsIn this prospective single centre cohort study in an intensive care setting patients aged ≥ 18 years with COVID-19 acute respiratory distress syndrome were assessed for concomitant microbial infections by longitudinal analysis of tracheobronchial secretions, bronchoalveolar lavages and blood. Our primary outcome was ventilator-free survival on day 28 in patients with and without clinically relevant superinfection. Further outcomes included the association of superinfection with ICU length of stay, incidence of bacteremia, viral reactivations, and fungal colonization.ResultsIn 45 critically ill COVID-19 patients, we identified 19 patients with superinfections (42.2%) by longitudinal analysis of 433 TBS, 35 BAL and 455 blood samples, respectively. On average, superinfections were detected on day 10 after ICU admission. The most frequently isolated clinically relevant bacteria were Enterobacteriaceae, Streptococcus pneumoniae, and Pseudomonas aeruginosa.Ventilator-free survival was substantially lower in patients with superinfection (subhazard ratio 0.37, 95%-CI 0.15-0.90, p=0.028). Patients with pulmonary superinfections more often had bacteraemia, virus reactivations, yeast colonization, and needed ICU treatment for a significantly longer time.ConclusionsThe detection of superinfections was frequent and associated with reduced ventilator-free survival. Despite empirical antibiotic therapy, superinfections lead to an extended ICU stay in COVID 19 patients. Longitudinal microbiological sampling in COVID-19 patients could allow targeted antimicrobial therapy, and therefore minimize the use of broad-spectrum and reserve antibiotics.
Productivity loss associated with physical impairment in a contemporary small-scale subsistence population
Authors: Stieglitz Jonathan , Hooper Paul L. , Trumble Benjamin C. , Kaplan Hillard , Gurven Michael D. 
Published: September 2020

AbstractHumans experience unique physical impairments with potentially severe economic consequences. Quantifying the burden of impairment in subsistence populations is critical for understanding selection pressures underlying strategies that minimize risk of production deficits. We examine among forager-horticulturalists whether compromised bone strength (indicated by vertebral fracture and lower bone mineral density, BMD) is associated with diminished subsistence involvement. We estimate the magnitude of productivity losses associated with compromised bone strength. Fracture is associated with cessation of hunting, tree chopping and walking long distances, but not tool manufacture. Age-specific productivity losses from hunting cessation related to fracture and lower BMD are substantial: ∼397 lost kcals/day, with expected future losses of up to 1.88 million kcals (22% of expected production). Productivity loss is thus substantial for high strength and endurance tasks. Determining the extent to which impairment obstructs productivity in contemporary subsistence populations improves the ability to infer consequences of impairment over human evolution.