bluuebunny/crossref_metadata_2025_split huggingface dataset:
ASSESSING VACCINATION STRATEGIES FOR THE COVID-19 EPIDEMIC IN MINAS GERAIS (BRAZIL)
Authors: Marchesin Marcelo , Sabeti Mehran 
Published: April 2021

AbstractIn this work we analyze the effectiveness of vaccination strategies for the COVID-19 epidemic in the Brazilian state of Minas Gerais. Firstly we study the effectiveness of general vaccination in the decreasing of the number of infected individuals using a traditional non structured SEIR model. Secondly we consider an age-structured SEIR model with 3 age groups (youngster, adult and elderly) and we analyze the current strategy in the Brazilian state of Minas Gerais, of focusing the vaccination on the elderly group. We conclude by showing this strategy to be mistaken and that a vaccination focusing on the age group of the adults would be much more efficient in decreasing the total number of infected individuals.
A versatile, fast and unbiased method for estimation of gene-by-environment interaction effects on biobank-scale datasets
Authors: Khan Mohammad , Di Scipio Matteo , Judge Conor , Perrot Nicolas , Chong Michael , Mao Shihong , Di Shuang , Nelson Walter , Petch Jeremy , Paré Guillaume 
Published: April 2021

AbstractCurrent methods to evaluate gene-by-environment (GxE) interactions on biobank-scale datasets are limited. MonsterLM enables multiple linear regression on genome-wide datasets, does not rely on parameters specification and provides unbiased estimates of variance explained by GxE interaction effects. We applied MonsterLM to the UK Biobank for eight blood biomarkers (N=325,991), identifying significant genome-wide interaction variance with waist-to-hip ratio for five biomarkers, with variance explained by interactions ranging from 0.11 to 0.58. 48% to 94% of GxE interaction variance can be attributed to variants without significant marginal association with the phenotype of interest. Conversely, for most traits, >40% of interaction variance was explained by less than 5% of genetic variants. We observed significant improvements in polygenic score prediction with incorporation of GxE interactions in four biomarkers. Our results imply an important contribution of GxE interaction effects, driven largely by a restricted set of variants distinct from loci with strong marginal effects.
Chronic kidney disease in Low- and Middle- Income Countries: Protocol for a systematic review of diagnostic and prognostic models
Authors: Ascencio Edson J , Aparcana-Granda Diego J , Carrillo-Larco Rodrigo M 
Published: April 2021

ABSTRACTBackgroundChronic Kidney Disease (CKD) is a highly prevalent condition with a large disease burden globally. In low- and middle-income countries (LMIC) the CKD screening challenges the health system. This systematic and comprehensive search of all CKD diagnostic and prognostic models in LMIC will inform screening strategies in LMIC following a risk-based approach.ObjectiveTo summarize all multivariate diagnostic and prognostic models for CKD in adults in LMIC.MethodsSystematic review. Without date or language restrictions we will search Embase, Medline, Global Health (these three through Ovid), SCOPUS and Web of Science. We seek multivariable diagnostic or prognostic models which included a random sample of the general population. We will screen titles and abstracts; we will then study the selected reports. Both phases will be done by two reviewers independently. Data extraction will be performed by two researchers independently using a pre-specified Excel form (CHARMS model). We will evaluate the risk of bias with the PROBAST tool.ConclusionThis systematic review will provide the most comprehensive list and critical appraisal of diagnostic and prognostic models for CKD available for the general population in LMIC. This evidence could inform policies and interventions to improve CKD screening in LMIC following a risk-based approach, maximizing limited resources and reaching populations with limited access to CKD screening tests. This systematic review will also reveal methodological limitations and research needs to improve CKD diagnostic and prognostic models in LMIC.
SARS-CoV-2 virus transfers to skin through contact with contaminated solids
Authors: Behzadinasab Saeed , Chin Alex W.H. , Hosseini Mohsen , Poon Leo L.M. , Ducker William A. 
Published: April 2021

AbstractTransfer of SARS-CoV-2 from solids to fingers is one step in infection via contaminated solids, and the possibility of infection from this route has driven calls for increased frequency of handwashing during the COVID-19 pandemic. To analyze this route of infection, we measured the percentage of SARS-CoV-2 that was transferred from a solid to an artificial finger. A droplet of SARS-CoV-2 suspension (1 µL) was placed on a solid, and then artificial skin was briefly pressed against the solid with a light force (3 N). Transfer from a variety of solids was detected, and transfer from the non-porous solids, glass, stainless steel, and Teflon, was substantial (13-16 %) when the droplet was still wet. Transfer still occurred after the droplet evaporated, but it was smaller. We found a lower level of transfer from porous solids but did not find a significant effect of solid wettability for non-porous solids.
Outcome Disparities by Insurance Plan and Educational Attainment in Patients with Atrial Fibrillation
Authors: Apiyasawat Sirin , Thongsri Tomon , Jongpiputvanich Kulyot , Krittayaphong Rungroj ,   for the COOL-AF Investigators
Published: April 2021

AbstractObjectivesDespite efforts to cut poverty, improve public health, and raise educational attainment, countries still suffer from disparities. Since 2002, Thailand has successfully implemented the Universal Health Coverage Scheme (UCS) to eradicate health care access inequity. Here, we explored the interlink between insurance plan, educational attainment, and adverse clinical outcomes in the national registry of patients with atrial fibrillation (AF) in Thailand.DesignA nationwide prospective multicenter cohort of non-valvular 3402 AF.Primary OutcomesPatients were followed for 36 months for primary outcomes of all-cause mortality, ischemic stroke, and major bleeding. Survival analysis was performed using restricted mean survival time (RMST) and adjusted with multiple covariates.ResultsData from 3026 AF patients (mean age 67, 59% male) were analyzed. The mean CHA2DS2VASc and HASBLED scores were 3.0 (SD 1.7) and 1.5 (SD 1.0) respectively. Most of the patients attained the elementary level of education (N=1739, 57.4%). The major health insurance plans were Civil Servant Medical Benefit Scheme (CSMBS; N=1397, 46.2%) and UCS (N=1333, 44.1%). After 36 months of follow-up, 248 patients died (8.2%), 95 suffered from ischemic stroke (3.1%), and 136 suffered from major bleeding (4.5%). AF patients with no formal education lost 1.78 months before they died (adjusted RMST difference -1.78; 95% CI, -3.25 to -0.30; P =.02) and 1.04 months before they developed ischemic stroke (adjusted RMST difference -1.04; 95% CI, -2.03 to -0.04; P =.04) compared to those with higher education. Educational attainment level was not associated with major bleeding. Across all types of insurance plan, RMSTs to all three clinical outcomes were essentially similar.ConclusionEducation attainment level was independently associated with all-cause mortality and ischemic stroke in AF patients.Health insurance plans were not associated with adverse clinical outcomes.Clinical Trial RegistrationThai Clinical Trial Registration; Study ID: TCTR20160113002Strengths and limitations of this studyThe study links two of the most important of sociodemographic factors, education and health insurance plan, and clinical outcomes of atrial fibrillation (AF), one of the most common cardiovascular conditions.Data is derived from a large prospective and nationwide cohort.The study evaluates healthcare quality in universal health coverage system.Causal relationship cannot be assumed from a cohort trial.Enrollment took place in the medical center, thus, excluding patients who could not access the healthcare facilities.
Asymmetric effects of acute stress on cost and benefit learning
Authors: Voulgaropoulou Stella , Fauzani Fasya , Pfirrmann Janine , Vingerhoets Claudia , van Amelsvoort Thérèse , Hernaus Dennis 
Published: April 2021

AbstractStressful events trigger a complex physiological reaction – thefight-or-flightresponse – that can hamper flexible decision-making. Inspired by key neural and peripheral characteristics of the fight-or-flight response, here we ask whether acute stress changes how humans learn about costs and benefits. Participants were randomly exposed to an acute stress or no-stress control condition after which they completed a cost-benefit reinforcement learning task. Acute stress improved learning to maximize benefits (monetary rewards) relative to minimising energy expenditure (grip force). Using computational modelling, we demonstrate that costs and benefits can exert asymmetric effects on decisions when prediction errors that convey information about the reward value and cost of actions receive inappropriate importance; a process associated with distinct alterations in pupil size fluctuations. These results provide new insights into learning strategies under acute stress – which, depending on the context, may be maladaptive or beneficial - and candidate neuromodulatory mechanisms that could underlie such behaviour.
Deprivation and Exposure to Public Activities during the COVID-19 Pandemic in England and Wales
Authors: Beale Sarah , Braithwaite Isobel , Navaratnam Annalan M D , Hardelid Pia , Rodger Alison , Aryee Anna , Byrne Thomas , Erica Fong Wing Lam , Fragaszy Ellen , Geismar Cyril , Kovar Jana , Nguyen Vincent , Patel Parth , Shrotri Madhumita , Aldridge Robert W , Hayward Andrew , Michie Susan , Wijlaars Linda , Nastouli Eleni , Spyer Moira , Killingley Ben , Cox Ingemar , Lampos Vasileios , McKendry Rachel A , Cheng Tao , Liu Yunzhe , Johnson Anne M , Gibbs Jo , Gilson Richard 
Published: April 2021

AbstractBackgroundDifferential exposure to public activities and non-household contacts may contribute to stark deprivation-related inequalities in SARS-CoV-2 infection and outcomes, but has not been directly investigated. We set out to investigate whether participants in Virus Watch – a large community cohort study based in England and Wales – reported different levels of exposure to public activities and non-household contacts during the Autumn-Winter phase of the COVID-19 pandemic according to postcode-level socioeconomic deprivation.MethodsParticipants (n=20120-25228 across surveys) reported their daily activities during three weekly periods in late November 2020, late December 2020, and mid-February 2021. Deprivation was quantified based on participants’ postcode of residence using English or Welsh Indices of Multiple Deprivation quintiles. We used Poisson mixed effect models with robust standard errors to estimate the relationship between deprivation and risk of exposure to public activities during each survey period.ResultsRelative to participants in the least deprived areas, participants in the most deprived areas persistently exhibited elevated risk of exposure to vehicle sharing (aRR range across time points 1.73-8.52), public transport (aRR 3.13-5.73), work or education outside of the household (aRR 1.09-1.21), essential shops (aRR 1.09-1.13) and non-household contacts (aRR 1.15-1.19) across multiple survey periods.ConclusionDifferential exposure to essential public activities in deprived communities is likely to contribute to inequalities in infection risk and outcomes during the COVID-19 pandemic. Public health interventions to reduce exposure during essential activities and financial and practical support to enable low-paid workers to stay at home during periods of intense transmission may reduce COVID-related inequalities.
Clinical validation of RCSMS: a rapid and sensitive CRISPR-Cas12a test for the molecular detection of SARS-CoV-2 from saliva
Authors: del Prado Joaquín Abugattás Núñez , Reyes Angélica Quintana , La Torre Juan Blume , Gutiérrez Loli Renzo , Pinzón Olejua Alejandro , Chamorro Chirinos Elena Rocío , Loza Mauricio Félix Antonio , Maguiña Jorge L. , Leon Julio , Rodríguez Aliaga Piere , Málaga Trillo Edward 
Published: April 2021

ABSTRACTEarly detection of SARS-CoV-2 using molecular techniques is paramount to the fight against COVID-19. Due to its high sensitivity and specificity, RT-qPCR is the “gold standard” method for this purpose. However, its technical requirements, processing time and elevated costs hamper its use towards massive and timely molecular testing for COVID-19 in rural and socioeconomically deprived areas of Latin America. The advent and rapid evolution of CRISPR-Cas technology has boosted the development of new pathogen detection methodologies. Recently, DETECTR -a combination of isothermal RT-LAMP amplification and Cas12a-mediated enzymatic detection-has been successfully validated in the Netherlands and the USA as a rapid and low-cost alternative to RT-qPCR for the detection of SARS-CoV-2 from nasopharyngeal swabs. Here, we evaluated the performance of RCSMS, a locally adapted variant of DETECTR, to ascertain the presence of SARS-CoV-2 in saliva samples from 276 patients in two hospitals in Lima, Perú (current status over a total of 350 samples). We show that a low-cost thermochemical treatment with TCEP/EDTA is sufficient to inactivate viral particles and cellular nucleases in saliva, eliminating the need to extract viral RNA with commercial kits, as well as the cumbersome nasopharyngeal swab procedure and the requirement of biosafety level 2 laboratories for molecular analyses. Our clinical validation shows that RCSMS detects up to 5 viral copies per reaction in 40 min, with sensitivity and specificity of 93.8% and 99.0% in the field, respectively, relative to RT-qPCR. Since CRISPR-Cas biosensors can be easily reprogrammed by using different guide RNA molecules, RCSMS has the potential to be quickly adapted for the detection of new SARS-CoV-2 variants. Notably, estimation of its negative and positive predictive values suggests that RCSMS can be confidently deployed in both high and low prevalence settings. Furthermore, our field study validates the use of lateral flow strips to easily visualize the presence of SARS-CoV-2, which paves the way to deploy RCSMS as a “point of care” test in environments with limited access to state-of-the-art diagnostic laboratories. In sum, RCSMS is a fast, efficient and inexpensive alternative to RT-qPCR for expanding COVID-19 testing capacity in low- and middle-income countries.
Building Back Better after COVID-19: a systematic scoping review of wicked problems affecting developed countries and implications for global governance
Authors: van Kessel Robin , Li Han Wong Brian 
Published: April 2021

AbstractThe COVID-19 pandemic is a textbook example of a ‘wicked problem’, one which is complex, open-ended, unpredictable, or intractable and seems resistant to any solution. This presents a window of opportunity to explore other wicked problems and their implications after the pandemic. A systematic scoping review was conducted to investigate the COVID-19 aftermath and identify public health topics which may be of great significance in the years to come. Through the adoption of three megadrivers as fundamental drivers of change (globalisation, demographic change, and digitalisation), it narratively explored how different wicked problems – and the driving mechanisms which sustain them – persist. It further explored the implications of these public health topics on global (health) governance. While the wicked problems mapped in this article show a large variance in where their apparent roots lie, they share one factor in common: health. These wicked problems must be first and foremost addressed if we as a globalised world are to successfully and sustainably build back better from COVID-19.Summary BoxWhat is already known?-COVID-19 is a textbook example of a wicked problem; a problem that is complex, open-ended, unpredictable, or intractable and seems resistant to any solution;-Digitalisation, globalisation, and demographic change are seen as the three megadrivers of change and are theorised to create and sustain modern wicked problems;-The megadrivers respectively have complex relationships with health; this includes both positive and negative associations.What are the new findings?-A series of wicked problems exist in multiple domains of society that continue to obstruct the progress of the 2030 Agenda for Sustainable Development;-These wicked problems each have roots in the three megadrivers: digitalisation, globalisation, and demographic change;-There exists a complex interrelation between the megadrivers, wicked problems, and health.What do the new findings imply?-It currently remains unclear to what extent wicked problems and megadrivers respectively affect health outcomes; therefore, further research is indicated;-A ‘once in a generation’ opportunity has presented itself to build back better from the COVID-19 pandemic by addressing the existing wicked problems; therefore, governance mechanisms should follow and adapt accordingly;-Wicked problems have bidirectional implications for modern policy; this has created an environment for wicked problems to manifest and sustain themselves, which in turn produce further policies that sustain wicked problems.
Detecting in-school transmission of SARS-CoV-2 from case ratios and documented clusters
Authors: Johnson Kaitlyn E. , Lachmann Michael , Stoddard Madison , Pasco Remy , Fox Spencer J. , Meyers Lauren Ancel , Chakravarty Arijit 
Published: April 2021

AbstractClaims that in-person schooling has not amplified SARS-CoV-2 transmission are based on similar infection rates in schools and their surrounding communities and limited numbers of documented in-school transmission events. Simulations assuming high in-school transmission suggest that these metrics cannot exclude the possibility that transmission in schools exacerbated overall pandemic risks.
Response to Polygenic Risk: Results of the MyGeneRank Mobile Application-Based Coronary Artery Disease Study
Authors: Muse Evan D. , Chen Shang-Fu , Liu Shuchen , Fernandez Brianna , Schrader Brian , Molparia Bhuvan , León André Nicolás , Lee Raymond , Pubbi Neha , Mejia Nolan , Ren Christina , El-kalliny Ahmed , Montes de Oca Ernesto Prado , Aguilar Hector , Ghoshal Arjun , Dias Raquel , Evans Doug , Chen Kai-Yu , Zhang Paris , Wineinger Nathan E , Spencer Emily G. , Topol Eric J. , Torkamani Ali 
Published: April 2021

AbstractThe degree to which polygenic risk scores (PRS) influence preventive health is the subject of debate, with few prospective studies completed to date. We developed a smartphone application for the prospective and automated generation, communication, and electronic capture of response to a PRS for coronary artery disease (CAD). We evaluated self-reported actions taken in response to personal CAD PRS information, with special interest in the initiation of lipid lowering therapy (NCT03277365). 20% of high genetic risk (n=95) vs 7.9% of low genetic risk individuals (n=101) initiated lipid lowering therapy at follow-up (p-value = 0.002). The initiation of both statin and non-statin lipid lowering therapy was associated with degree of genetic risk – 15.2% (n=92) vs 6.0% (n=100) for statins (p-value = 0.018) and 6.8% (n=118) vs 1.6% (n=123) for non-statins (p-value = 0.022) in high vs low genetic risk, respectively. Overall, degree of genetic risk was associated with use of any lipid lowering therapy at follow-up - 42.4% (n=132) vs 28.5% (n=130) (p-value = 0.009). We also find that CAD PRS information is perceived to be understandable, actionable, and does not induce health anxiety.
Fluoxetine targets an allosteric site in the enterovirus 2C AAA+ ATPase and stabilizes the hexameric complex
Authors: Hurdiss Daniel L. , El Kazzi Priscila , Bauer Lisa , Papageorgiou Nicolas , Ferron François P. , Donselaar Tim , van Vliet Arno L.W. , Canard Bruno , Decroly Etienne , Brancale Andrea , Zeev-Ben-Mordehai Tzviya , Förster Friedrich , van Kuppeveld Frank J.M , Coutard Bruno 
Published: April 2021

AbstractThe enterovirus genus encompasses many clinically important human pathogens such as poliovirus, coxsackieviruses, echoviruses, numbered enteroviruses and rhinoviruses. These viruses are the etiological agents of several human diseases, including hand-foot-and-mouth disease, neonatal sepsis, encephalitis, meningitis, paralysis and respiratory infections. There is an unmet need for antivirals to treat these diseases. The non-structural protein 2C is a AAA+ helicase and plays a key role in viral replication. As such, it is an attractive target for antiviral drug development. Several repurposing screens with FDA-approved drugs have identified 2C-targeting compounds such as fluoxetine and dibucaine, but the molecular basis of 2C inhibition has remained enigmatic. Here we present the 1.5 Å resolution crystal structure of the soluble fragment of coxsackievirus B3 2C protein in complex with (S)-fluoxetine (SFX), which reveals a conserved, hydrophobic drug-binding pocket which is distal to the ATP binding site. To decipher the molecular mechanism of inhibition by fluoxetine and other 2C-targeting compounds, we engineered a soluble, hexameric and ATPase competent 2C protein. Using this system, we show that SFX, dibucaine, HBB and guanidine hydrochloride inhibit 2C ATPase activity in a dose-dependent manner. Moreover, using cryo-EM analysis, we demonstrate that SFX and dibucaine lock 2C in a defined hexameric state, rationalizing their mode of inhibition and allowing us to generate the first reconstruction of the oligomeric complex. Taken together, these results provide important structural and mechanistic insights into 2C inhibition and provide a robust engineering strategy which can be used for structural, functional and drug-screening analysis of 2C proteins from current or future enteroviruses.
Frontal cortex learns to add evidence across modalities
Authors: Coen Philip , Sit Timothy P.H. , Wells Miles J , Carandini Matteo , Harris Kenneth D 
Published: April 2021

SummaryTo make accurate perceptual decisions, the brain often combines information across sensory modalities. For instance, localizing objects by integrating their image and sound. However, the cortical substrates underlying this audiovisual integration remain uncertain. Here, we show that mouse frontal cortex combines auditory and visual evidence; that this combination is additive, mirroring behavior; and that it evolves with learning. Scanning optogenetic inactivation demonstrated that inactivating frontal cortex impaired choices based on either sensory modality. Recordings from >10,000 neurons indicated that after task learning, activity in frontal area MOs (secondary motor cortex) encodes an additive combination of visual and auditory signals, consistent with the mice’s behavioral strategy. An accumulator model applied to these sensory representations reproduced both the observed choices and reaction times. These results indicate that frontal cortex adapts through learning to combine evidence across sensory cortices, providing a signal that is transformed into a binary decision by a downstream accumulator.