bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Non-traditional Epidemic Disease Risk Factors associated to major Health Events from WHO and World Bank Open Data
Authors: Lugo-Robles Roberta , Garges Eric C. , Olsen Cara H. , Brett-Major David M. 
Published: June 2020

AbstractObjectivesHealth events emerge from a multifactorial milieu involving host, community, environment, and pathogen factors. Therefore, developing accurate forecasting models to improve epidemic prediction towards better prevention and capabilities management is a complex task. Here, we describe an exploratory analysis to identify non-health risk factors that could improve the forecast and events risk signals using a feasible and practical approach by combining surveillance report data with non-health data from open data sources.MethodsA line listing was developed using information from the World Health Organization Disease Outbreaks News from 2016-2018. A database was created merging the line listing data with non-health indicators from the World Bank. Poisson regression models employing forward imputations were used to establish relationships and predict values over the dependent variable (health event frequency); which are the health events reported by each country to WHO during 2016-2018.FindingsThe resulting regression model provided evidence that changes in non-health factors important to community experiences impact the risk of the number of major health events that a country could experience. Three non-health indicators (extrinsic factors) were associated significantly to event frequency (population urban change, gross domestic product change per capita—a novel factor, and average forest area). An exploratory analysis of the current COVID-19 pandemic suggested similar associations, but confounding by global disease burden is likely.ConclusionContinued development of forecasting approaches capturing available whole-of-society extrinsic factors (non-health factors); could improve the risk management process through earlier hazard identification, and as importantly inform strategic decision processes in multisectoral strategies to preventing, detecting, and responding to pandemic-threat events.
On the increasing role of older adolescents and younger adults during the SARS-CoV-2 epidemic in Mexico, April 20 – May 24, 2020
Authors: Stern D , Lajous M , Goldstein E 
Published: June 2020

AbstractBackgroundThe SARS-CoV-2 epidemic in Mexico is growing, and there is uncertainty regarding the role that different age groups play in propagating the epidemic.MethodsWe used data on hospitalizations with confirmed SARS-CoV-2 infection from the Mexican Ministry of Health in ten 5-year age groups: 10-14through 55-59 years. For each age group g, we computed the proportion E(g) of individuals in that age group among all hospitalized cases aged 10-59 years during the early period (between April 20 – May 3, 2020), the corresponding proportion L(g) during the later periods (May 11-24), as well as the relative risk RR(g)= L(g)/E(g). For each pair of age groups g1,g2, RR(g1)>RR(g2) is interpreted as a relative increase in SARS-CoV-2 infections in the age group g1 compared with g2 for the later vs. early period.ResultsThe highest RR estimates belong to persons aged 15-19 years (RR=1.93(95% CI (1.19,3.12)) and 20-24 years (RR=1.40(1.07,1.83)). The RR estimates in persons aged over 30 years were significantly lower compared to persons aged 15-24 years.ConclusionsOur results suggest a temporal increase in the incidence of SARS-CoV-2 infection in older adolescents and younger adults compared to other age groups. Targeted interventions, particularly public health messaging at those age groups to increase knowledge and risk awareness may be considered.
A Machine Learning Study to Improve Surgical Case Duration Prediction
Authors: Huang Ching-Chieh , Lai Jesyin , Cho Der-Yang , Yu Jiaxin 
Published: June 2020

AbstractPredictive accuracy of surgical case duration plays a critical role in reducing cost of operation room (OR) utilization. The most common approaches used by hospitals rely on historic averages based on a specific surgeon or a specific procedure type obtained from the electronic medical record (EMR) scheduling systems. However, low predictive accuracy of EMR leads to negative impacts on patients and hospitals, such as rescheduling of surgeries and cancellation. In this study, we aim to improve prediction of operation case duration with advanced machine learning (ML) algorithms. We obtained a large data set containing 170,748 operation cases (from Jan 2017 to Dec 2019) from a hospital. The data covered a broad variety of details on patients, operations, specialties and surgical teams. Meanwhile, a more recent data with 8,672 cases (from Mar to Apr 2020) was also available to be used for external evaluation. We computed historic averages from EMR for surgeon- or procedure-specific and they were used as baseline models for comparison. Subsequently, we developed our models using linear regression, random forest and extreme gradient boosting (XGB) algorithms. All models were evaluated with R-squre (R2), mean absolute error (MAE), and percentage overage (case duration>prediction + 10 % & 15 mins), underage (case duration<prediction - 10 % & 15 mins) and within (otherwise). The XGB model was superior to the other models by having higherR2(85 %) and percentage within (48 %) as well as lowerMAE(30.2 mins). The total prediction errors computed for all the models showed that the XGB model had the lowest inaccurate percent (23.7 %). As a whole, this study applied ML techniques in the field of OR scheduling to reduce medical and financial burden for healthcare management. It revealed the importance of operation and surgeon factors in operation case duration prediction. This study also demonstrated the importance of performing an external evaluation to better validate performance of ML models.
Plasma levels of soluble ACE2 are associated with sex, Metabolic Syndrome, and its biomarkers in a large cohort, pointing to a possible mechanism for increased severity in COVID-19
Authors: Kornilov Sergey A. , Lucas Isabelle , Jade Kathleen , Dai Chengzhen L. , Lovejoy Jennifer C. , Magis Andrew T. 
Published: June 2020

AbstractWe examined the associations between plasma concentrations of soluble ACE2 and biomarkers of Metabolic Syndrome in a large (N=2,051) sample of individuals who participated in a commercial wellness program and who underwent deep molecular phenotyping. sACE2 levels were significantly higher in men, compared to women, and in individuals with Metabolic Syndrome, compared to controls. sACE2 levels showed reliable associations with all individuals components of Metabolic Syndrome, including obesity, hypertension, insulin resistance, hyperlipidemia, and as well as markers of liver damage. This profile of associations was statistically significantly stronger in men, compared to women, and points to preexisting cardiometabolic conditions as possible risk factors for increased severity of symptoms in some COVID-19 patients through increased expression of ACE2 in the liver.
Estimating the Impact of Control Measures to Prevent Outbreaks of COVID-19 Associated with Air Travel into a COVID-19-free country: A Simulation Modelling Study
Authors: Wilson Nick , Baker Michael G , Eichner Martin 
Published: June 2020

AbstractAimsWe aimed to estimate the risk of COVID-19 outbreaks associated with air travel from a country with a very low prevalence of COVID-19 infection (Australia) to a COVID-19-free country (New Zealand; [NZ]), along with the likely impact of various control measures for passengers and cabin crew.MethodsA stochastic version of the SEIR model CovidSIM v1.1, designed specifically for COVID-19 was utilized. It was populated with data for both countries and parameters for SARS-CoV-2 transmission and control measures. We assumed one Australia to NZ flight per day.ResultsWhen no interventions were in place, an outbreak of COVID-19 in NZ was estimated to occur after an average time of 1.7 years (95% uncertainty interval [UI]: 0.04-6.09). However, the combined use of exit and entry screening (symptom questionnaire and thermal camera), masks on aircraft and two PCR tests (on days 3 and 12 in NZ), combined with self-reporting of symptoms and contact tracing and mask use until the second PCR test, reduced this risk to one outbreak every 29.8 years (0.8 to 110). If no PCR testing was performed, but mask use was used by passengers up to day 15 in NZ, the risk was one outbreak every 14.1 years. However, 14 days quarantine (NZ practice in May 2020), was the most effective strategy at one outbreak every 34.1 years (0.06 to 125); albeit combined with exit screening and mask use on flights.ConclusionsPolicy-makers can require multi-layered interventions to markedly reduce the risk of importing the pandemic virus into a COVID-19-free nation via air travel. There is potential to replace 14-day quarantine with PCR testing or interventions involving mask use by passengers in NZ. However, all approaches require continuous careful management and evaluation.
ROBOCOV: An affordable open-source robotic platform for SARS-CoV-2 testing by RT-qPCR
Authors: Villanueva-Cañas José Luis , Gonzalez-Roca Eva , Unanue Aitor Gastaminza , Titos Esther , Martínez Yoldi Miguel Julián , Vergara Gómez Andrea , Puig Butillé Joan Antón 
Published: June 2020

ABSTRACTCurrent global pandemic due to the SARS-CoV-2 has struggled and pushed the limits of global health systems. Supply chain disruptions and scarce availability of commercial laboratory reagents have motivated worldwide actors to search for alternative workflows to cope with the demand.We have used the OT-2 open-source liquid-handling robots (Opentrons, NY), RNA extraction and RT-qPCR reagents to set-up a reproducible workflow for RT-qPCR SARS-CoV-2 testing. We developed a framework with a template and several functions and classes that allow the creation of customized RT-qPCR automated circuits. As a proof of concept, we provide data obtained by a fully-functional tested code using the MagMax™ Pathogen RNA/DNA kit and the MagMax™ Viral/Pathogen II kit (Thermo Fisher Scientific, MA) on the Kingfisher™ Flex instrument (Thermo Fisher Scientific, MA). With these codes available is easy to create new stations or circuits from scratch, adapt existing ones to changes in the experimental protocol, or perform fine adjustments to fulfil special needs.The affordability of this platform makes it accessible for most laboratories and hospitals with a bioinformatician, democratising automated SARS-CoV-2 PCR testing and increasing, temporarily or not, the capacity of carrying out tests. It also confers flexibility, as this platform is not dependant on any particular commercial kit and can be quickly adapted to protocol changes or other special needs.
A non-enveloped arbovirus released in lysosome-derived extracellular vesicles induces super-infection exclusion
Authors: Labadie Thomas , Roy Polly 
Published: June 2020

AbstractRecent developments on extracellular vesicles (EVs) containing multiple virus particles challenge the rigid definition of non-enveloped viruses. However, how non-enveloped viruses hijack cell machinery to promote non-lytic release in EVs, and their functional roles, remain to be clarified. Here we used Bluetongue virus (BTV) as a model of a non-enveloped arthropod-borne virus and observed that the majority of viruses are released in EVs, bothin vitroand in the blood of infected animals. Based on the cellular proteins detected in these EVs, and use of inhibitors targeting the cellular degradation process, we demonstrated that these extracellular vesicles are derived from secretory lysosomes, in which the acidic pH is neutralized upon the infection. Moreover, we report that secreted EVs are more efficient than free-viruses for initiating infections, but that they trigger super-infection exclusion that only free-viruses can overcome.Author summaryRecent discoveries of non-enveloped virus secreted in EVs opened the door to new developments in our understanding of the transmission and pathogenicity of these viruses. In particular, how these viruses hijack the host cellular secretion machinery, and the role of these EVs compared with free-virus particles remained to be explored. Here, we tackled these two aspects, by studying BTV, an emerging arthropod-borne virus causing epidemics worldwide. We showed that this virus is mainly released in EVs,in vivoand in the blood of infected animals, and that inhibition of the cell degradation machinery decreases the release of infectious EVs, but not free-virus particles. We found that BTV must neutralize the pH of lysosomes, which are important organelles of the cell degradation machinery, for efficient virus release in EVs. Our results highlight unique features for a virus released in EVs, explaining how BTV transits in lysosomes without being degraded. Interestingly, we observed that EVs are more infectious than free-virus particles, but only free-viruses are able to overcome the super-infection exclusion, which is a common cellular defense mechanism. In conclusion, our study stresses the dual role played by both forms, free and vesicular, in the virus life cycle.
Doxycycline has Distinct Apicoplast-Specific Mechanisms of Antimalarial Activity
Authors: Okada Megan , Guo Ping , Nalder Shai-anne , Sigala Paul A. 
Published: June 2020

AbstractDoxycycline (DOX) is a key antimalarial drug thought to killPlasmodiumparasites by blocking protein translation in the essential apicoplast organelle. Clinical use is primarily limited to prophylaxis due to delayed second-cycle parasite death at 1-3 μM serum concentrations. DOX concentrations >5 μM kill parasites with first-cycle activity but have been ascribed to off-target mechanisms outside the apicoplast. We report that 10 μM DOX blocks apicoplast biogenesis in the first cycle and is rescued by isopentenyl pyrophosphate, an essential apicoplast product, confirming an apicoplast-specific mechanism. Exogenous iron rescues parasites and apicoplast biogenesis from first-but not second-cycle effects of 10 μM DOX, revealing that first-cycle activity involves a metal-dependent mechanism distinct from the delayed-death mechanism. These results critically expand the paradigm for understanding the fundamental antiparasitic mechanisms of DOX and suggest repurposing DOX as a faster-acting antimalarial at higher dosing whose multiple mechanisms would be expected to limit parasite resistance.
The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator ofC. elegansspermatogenesis
Authors: Ragle James Matthew , Aita Abigail L. , Morrison Kayleigh N. , Martinez-Mendez Raquel , Saeger Hannah N. , Ashley Guinevere A. , Johnson Londen C. , Schubert Katherine A. , Shakes Diane C. , Ward Jordan D. 
Published: June 2020

AbstractIn sexually reproducing metazoans, spermatogenesis is the process by which uncommitted germ cells give rise to haploid sperm. Work in model systems has revealed mechanisms controlling commitment to the sperm fate, but how this fate is subsequently executed remains less clear. While studying the well-established role of the conserved nuclear hormone receptor transcription factor, NHR-23/NR1F1, in regulation ofC. elegansmolting, we discovered NHR-23/NR1F1 is also constitutively expressed in developing 1° spermatocytes and is a critical regulator of spermatogenesis. In this novel role, NHR-23/NR1F1 functions downstream of the canonical sex determination pathway. Degron-mediated depletion of NHR-23/NR1F1 within hermaphrodite or male germlines causes sterility due to an absence of functional sperm as depleted animals produce arrested primary spermatocytes rather than haploid sperm. These spermatocytes arrest in prometaphase I and fail to either progress to anaphase or attempt spermatid-residual body partitioning. They make sperm-specific membranous organelles (MOs) but fail to assemble their major sperm protein into fibrous bodies. NHR-23/NR1F1 appears to function independently of the known SPE-44 gene regulatory network, revealing the existence of an NHR-23/NR1F1-mediated module that regulates the spermatogenesis program.Summary StatementA well-characterized regulator ofC. elegansmolting also unexpectedly controls the spermatogenesis program; our work provides insights into the gene regulatory networks controlling spermatogenesis.
The arrival and spread of SARS-CoV2 in Colombia
Authors: Ramírez Juan David , Florez Carolina , Muñoz Marina , Hernández Carolina , Castillo Adriana , Gomez Sergio , Rico Angelica , Pardo Lisseth , Barros Esther C. , Castañeda Sergio , Ballesteros Nathalia , Martínez David , Vega Laura , Jaimes Jesús E. , Cruz-Saavedra Lissa , Herrera Giovanny , Patiño Luz H. , Teherán Aníbal A. , Gonzalez-Reiche Ana S. , Hernandez Matthew M. , Sordillo Emilia Mia , Simon Viviana , van Bakel Harm , Paniz-Mondolfi Alberto 
Published: June 2020

ABSTRACTWe performed phylogenomic analysis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) from 88 infected individuals across different regions of Colombia. Eleven different lineages were detected, suggesting multiple introduction events. Pangolin lineages B.1 and B.1.5 were the most frequent, with B.1 being associated with prior travel to high-risk areas.Article Summary LineWe sequenced 88 genomes of SARS-CoV2 from Colombia finding 11 lineages and eight different introduction events
Cost effective reusable gowns for routine use in hospital and laboratory: a necessity arising of COVID-19 Pandemic
Authors: Shahane-Kapse Priyanka , Patond Anjali , Deotale Vijayshri , Narang Rahul 
Published: June 2020

AbstractCOVID-19 pandemic caused by SARS-CoV-2 has started a paradigm shift in working in a hospital or laboratory and airborne precautions have become equally significant as universal blood and body fluid precautions. Use of PPE including surgical masks or N95FFR is becoming a norm and this has led to scarcity of PPE for healthcare workers. We have prepared gowns for healthcare and laboratory workers made from a reusable material and tested with various disinfectants and heat. The cloth could tolerate repeated exposures to heat, alcohol, hypochlorite and hydrogen peroxide, but was damaged by phenol. Since this impermeable material did not allow the air to pass, we used a cool vest made up of indigenous “Khadi” cloth with pockets containing phase change material. The cost of whole reusable assembly of gown and cap was Indian Rupees 250 (1USD=76INR). This can be used in healthcare workers in hospital and community as well as people in diagnostic and research laboratories as a cost effective PPE.
Angiotensin-converting enzyme (ACE1, ACE2) gene variants are associated with COVID19 severity depending on the hypertension status
Authors: Gómez Juan , Albaiceta Guillermo M , García-Clemente Marta , López-Larrea Carlos , Amado-Rodríguez Laura , Hermida Tamara , Enriquez Ana I. , Herrero Pablo , Melón Santiago , Alvarez-Argüelles Marta E. , Rojo-Alba Susana , Leal-Negredo Alvaro , Cuesta-Llavona Elías , Alvarez Victoria , Lorca Rebeca , Coto Eliecer 
Published: June 2020

AbstractBackgroundThe Angiotensin system is implicated in the pathogenesis of COVID19. First, ACE2 is the cellular receptor for SARS-COv-2, and expression of theACE2gene could regulate the individual’s susceptibility to infection. In addition, the balance between ACE1 and ACE activity has been implicated in the pathogenesis of respiratory diseases and could play a role in the severity of COVID19. FunctionalACE1/ACE2gene polymorphisms have been associated with the risk of cardiovascular and pulmonary diseases, and could thus also contribute to the outcome of COVID19.MethodsWe studied 204 COVID19 patients (137 non-severe and 67severe-ICU cases) and 536 age-matched controls. TheACE1insertion/deletion andACE2rs2285666 polymorphism were determined. Variables frequencies were compared between the groups by logistic regression. We also sequenced the ACE2 coding nucleotides in a group of patients.ResultsSevere COVID19 was associated with hypertension male gender (p<0.001), hypertension (p=0.006), hypercholesterolaemia (p=0.046), and the ACE1-DD genotype (p=0.049). In the multiple logistic regression hypertension (p=0.02, OR=2.26, 95%CI=1.12-4.63) and male gender (p=0.002; OR=3.15, 95%CI=1.56-6.66) remained as independent significant predictors of severity. TheACE2polymorphism was not associated with the disease outcome. TheACE2sequencing showed no coding sequence variants that could explain an increased risk of developing COVID19.ConclusionsAdverse outcome of COVID19 was associated with male gender, hypertension, hypercholesterolemia and theACE1genotype. TheACE1-I/D was a significant risk factor for severe COVID19, but the effect was dependent on the hypertensive status.
Plasma (1→3) β-d-glucan levels are associated with host inflammatory responses and predict adverse clinical outcomes in critical illness
Authors: Kitsios Georgios D. , Kotok Daniel , Yang Haopu , Finkelman Malcolm , Zhang Yonglong , Britton Noel , Guo Rui , Evankovich John W. , Bain William , Shah Faraaz , Zhang Yingze , Benos Panayiotis V. , McVerry Bryan J. , Morris Alison 
Published: June 2020

AbstractBackgroundThe fungal cell-wall constituent (1,3)-β-d-glucan (BDG) is a pathogen-associated molecular pattern (PAMP) that can stimulate innate immunity. We hypothesized that BDG from colonizing fungi in critically-ill patients may translocate into the systemic circulation and thus be associated with host inflammatory responses and outcomes.MethodsWe enrolled 453 mechanically-ventilated patients with acute respiratory failure with no evidence of invasive fungal infection (IFI). From serial plasma samples, we measured BDG, innate immunity and epithelial permeability biomarkers. From lower respiratory tract and stool samples we quantified bacterial and fungal DNA load using culture-independent techniques.ResultsA positive BDG test (>60pg/ml) at baseline was detected in 19% of patients. BDG levels were significantly associated with markers of innate immunity (interleukin-6, tumor necrosis factor receptor-1 and procalcitonin), epithelial barrier disruption (receptor for advanced glycation end-products and fatty-acid binding protein-2, for lung and gut respectively) and with higher probability of classification in an adverse prognosis hyperinflammatory subphenotype (all p<0.05). No differences in fungal or bacterial DNA load were found by BDG test positivity. Positive BDG testing was associated with higher incidence of acute kidney injury, fewer ventilator free days and worse 30-day survival (adjusted p<0.05). Patients with positive BDG test on follow-up sampling (>3 days from intubation) had higher mortality than patients with persistently negative test on follow-up (p<0.05).ConclusionsThis is the first study to demonstrate the prognostic role of BDG in critically ill patients with no evidence of IFI. Translocation of BDG into systemic circulation may contribute to inflammation and clinical outcomes.Funding supportNational Institutes of Health [K23 HL139987 (GDK); U01 HL098962 (AM); P01 HL114453 (BJM); R01 HL097376 (BJM); K24 HL123342 (AM); U01 HL137159 (DVM, PVB); R01 LM012087 (DVM, PVB); R01 HL142084 (JSL); R01 HL136143 (JSL); F32 HL137258 (JWE); F32 HL142172 (WB); K08 HS025455 (IJB); K23 GM122069 (FS)].