bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling transmission dynamics and effectiveness of worker screening programs for SARS-CoV-2 in pork processing plants
Authors: VanderWaal Kimberly , Black Lora , Hodge Judy , Bedada Addisalem , Dee Scott 
Published: March 2021

AbstractPork processing plants were apparent hotspots for SARS-CoV2 in the spring of 2020. As a result, the swine industry was confronted with a major occupational health, financial, and animal welfare crisis. The objective of this work was to describe the epidemiological situation within processing plants, develop mathematical models to simulate transmission in these plants, and test the effectiveness of routine PCR screening at minimizing SARS-CoV2 circulation. Cumulative incidence of clinical (PCR-confirmed) disease plateaued at ∼2.5% to 25% across the three plants studied here. For larger outbreaks, antibody prevalence was approximately 30% to 40%. Secondly, we developed a mathematical model that accounts for asymptomatic, pre-symptomatic, and background “community” transmission. By calibrating this model to observed epidemiological data, we estimated the initial reproduction number (R) of the virus. Across plants,Rgenerally ranged between 2 and 4 during the initial phase, but subsequently declined to ∼1 after two to three weeks, most likely as a result of implementation/compliance with biosecurity measures in combination with population immunity. Using the calibrated model to simulate a range of possible scenarios, we show that the effectiveness of routine PCR-screening at minimizing disease spread was far more influenced by testing frequency than by delays in results,R, or background community transmission rates. Testing every three days generally averted about 25% to 40% of clinical cases across a range of assumptions, while testing every 14 days typically averted 7 to 13% of clinical cases. However, the absolute number of additional clinical cases expected and averted was influenced by whether there was residual immunity from a previous peak (i.e., routine testing is implemented after the workforce had experienced an initial outbreak). In contrast, when using PCR-screening to prevent outbreaks or in the early stages of an outbreak, even frequent testing may not prevent a large outbreak within the workforce. This research helps to identify protocols that minimize risk to occupational safety and health and support continuity of business for U.S. processing plants. While the model was calibrated to meat processing plants, the structure of the model and insights about testing are generalizable to other settings where large number of people work in close proximity.
Real World Performance of SARS-CoV-2 Antigen Rapid Diagnostic Tests in Various Clinical Settings
Authors: Regev-Yochay Gili , Kriger Or , Beni Sharon , Rubin Carmit , Mina Michael J. , Mechnik Bella , Hason Sabrina , Biber Elad , Nadaf Bian , Kreiss Yitshak , Amit Sharon 
Published: March 2021

AbstractBackgroundSeveral uses of Antigen rapid diagnostic tests (Ag-RDT) have been suggested. Analytical studies reported high specificity yet with lower sensitivity for detecting SARS-CoV-2 compared to qRT-PCR. Here, we present the use of these tests as a decision support tool in several settings.MethodsSamples were collected for both Ag-RDT and qRT-PCR in three different clinical settings; 1. Symptomatic patients presenting at the Emergency Departments 2. Asymptomatic patients screened upon hospitalization and 3. Health-care workers (HCW) following SARS-CoV-2 exposure. Positive percent agreement (PPA), negative percent agreement (NPA), positive predictive value (PPV) and negative predictive value (NPV) were calculated. To estimate the association between Ct value, Ag-RDT and the number of days since SARS-CoV-2 exposure or symptomatic COVID-19, a mixed model was applied.ResultsA total of 5172 samples were obtained from 4595 individuals, with Ag-RDT and qRT-PCR results. Of these, 485 samples were positive by qRT-PCR. The PPA of Ag-RDT was greater for lower Ct values, reaching 93% in cases where Ct value was lower than 25 and 85% where Ct value was lower than 30. PPA was similar between symptomatic and asymptomatic individuals. The NPV and PPV were 96.8% and 99.1%, respectively. We observed a significant correlation between Ct value and time from infection onset (p<0.001). Lower Ct values were significantly associated with a positive Ag-RDT (p=0.01).ConclusionsAg-RDT can be used as a decision support tool in various clinical settings and play a major role in early detection of SARS-CoV-2 infected individuals, highly specific and with high sensitivity to the infectious stage of disease, whether symptomatic or asymptomatic.
RT-RC-PCR: a novel and highly scalable next-generation sequencing method for simultaneous detection of SARS-COV-2 and typing variants of concern
Authors: Mattocks Christopher , Ward Daniel , Mackay Deborah 
Published: March 2021

AbstractWe describe a novel assay method: reverse-transcription reverse-complement polymerase chain reaction (RT-RC-PCR), which rationalises reverse transcription and NGS library preparation into a single closed tube reaction. By simplifying the analytical process and cross-contamination risks, RT-RC-PCR presents disruptive scalability and economy while using NGS and LIMS infrastructure widely available across health service, institutional and commercial laboratories.We present a validation of RT-RC-PCR for the qualitative detection of SARS-CoV-2 RNA by NGS. The limit of detection is comparable to real-time RT-PCR, and no obvious difference in sensitivity was detected between extracted nasopharyngeal swab (NPS) RNA and native saliva samples.The end point measurement of RT-RC-PCR is NGS of amplified sequences within the SARS-CoV-2 genome; we demonstrated its capacity to detect different variants using amplicons containing delH69-V70 and N501Y, both of which emerged in the UK Variant of Concern B.1.1.7 in 2020.In summary, RT-RC-PCR has potential to facilitate accurate mass testing at disruptive scale and cost, with concurrent detection of variants of concern.
The Missing Link: A Closed Form Solution to the Kermack and Mckendrick Epidemic Model Equations
Authors: Duclos Ted , Reichert Tom 
Published: March 2021

ABSTRACTSusceptible–infectious–recovered (SIR) models are widely used for estimating the dynamics of epidemics. Such models project that containment measures “flatten the curve”, i.e., reduce but delay the peak in daily infections, cause a longer epidemic, and increase the death toll. These projections have entered common understanding; individuals and governments often advocate lifting containment measures such as social distancing to shift the peak forward, limit societal and economic disruption, and reduce mortality. It was, then, an extraordinary surprise to discover that COVID-19 pandemic data exhibit phenomenology opposite to the projections of SIR models. With the knowledge that the commonly used SIR equations only approximate the original equations developed to describe epidemics, we identified a closed form solution to the original epidemic equations. Unlike the commonly used approximations, the closed form solution replicates the observed phenomenology and quantitates pandemic dynamics with simple analytical tools for policy makers. The complete solution is validated using independently measured mobility data and accurately predicts COVID-19 case numbers in multiple countries.
A Two-Sample Robust Bayesian Mendelian Randomization Method Accounting for Linkage Disequilibrium and Idiosyncratic Pleiotropy with Applications to the COVID-19 Outcome
Authors: Wang Anqi , Liu Zhonghua 
Published: March 2021

ABSTRACTMendelian randomization (MR) is a statistical method exploiting genetic variants as instrumental variables to estimate the causal effect of modifiable risk factors on an outcome of interest. Despite wide uses of various popular two-sample MR methods based on genome-wide association study summary level data, however, those methods could suffer from potential power loss or/and biased inference when the chosen genetic variants are in linkage disequilibrium (LD), and also have relatively large direct effects on the outcome whose distribution might be heavy-tailed which is commonly referred to as the idiosyncratic pleiotropy phenomenon. To resolve those two issues, we propose a novel Robust Bayesian Mendelian Randomization (RBMR) model that uses the more robust multivariate generalizedt-distribution (Arellano-Valle and Bolfarine, 1995) to model such direct effects in a probabilistic model framework which can also incorporate the LD structure explicitly. The generalizedt-distribution can be represented as a Gaussian scaled mixture so that our model parameters can be estimated by the EM-type algorithms. We compute the standard errors by calibrating the evidence lower bound using the likelihood ratio test. Through extensive simulation studies, we show that our RBMR has robust performance compared to other competing methods. We also apply our RBMR method to two benchmark data sets and find that RBMR has smaller bias and standard errors. Using our proposed RBMR method, we find that coronary artery disease is associated with increased risk of critically ill coronavirus disease 2019 (COVID-19). We also develop a user-friendly R packageRBMR(https://github.com/AnqiWang2021/RBMR) for public use.
Efficacy of Nitazoxanide in reducing the viral load in COVID-19 patients. Randomized, placebo-controlled, single-blinded, parallel group, pilot study.
Authors: Silva Marcelo , Espejo Andrés , L Pereyra María , Lynch Martín , Thompson Marcos , Taconelli Hernán , Baré Patricia , J Pereson Matías , Garbini Marcelo , Crucci Pablo , Enriquez Diego 
Published: March 2021

AbstractThe fast spread of COVID-19 has overcrowded Public Health Systems facilities in major countries due to the large number of seriously ill patients, particularly those requiring admission to intensive care units. Reducing viral load, along with other recommended epidemiological measures, such as social distancing and home confinement, can in time significantly help to reduce the infection R0 (Basic Reproductive Rate) and then mitigate disease burden. Early negativization or otherwise reduction of the viral load can potentially diminish disease severity, resulting in a better-controlled public health response, avoiding collapse of healthcare systems. Nitazoxanide, a widely used thiazolide approved by the FDA as an antiparasitic drug, also approved in Brazil for Norovirus and Rotavirus treatments, has an excellent safety record for a variety of indications. Nitazoxanide exhibits activity in vitro against MERS-CoV and other coronaviruses; and a specific antiviral effect (in micro molar doses) against SARS-CoV-2. The objective of this study was to evaluate the efficacy and safety of Nitazoxanide in reducing the SARS-COV 2 viral load within 7 days of treatment in respiratory samples from COVID-19-infected patients with mild to moderate disease, compared to placebo. An interim analysis showed that the ratio of patients with a viral load reduction ≥ 35% from baseline up to day 7 of treatment was significantly greater for Nitazoxanide compared to placebo (47.8% vs. 15.4%; Δ 34.6%; 95% CI: 64.7; 4.6: p = 0.037).KEY POINTSState of the ArtDifferent studies conclude that viral load (VL) would correlate with morbidity, mortality and contagiousness of COVID-19.Early negativization or reduction of the viral load can potentially reduce the severity of this disease.In vitro data demonstrated a specific antiviral effect of Nitazoxanide for SARS-CoV-2.Article contributionNitazoxanide showed a statistically significant difference versus placebo in the number of patients who had their viral load reduced by at least 35% in mild to moderate COVID-19 disease.The observed antiviral effect in vitro would seems to be verified in patients with mild to moderate COVID-19 infection, which should be confirmed by studies with a larger cohort of patients.
Quantification of seizure termination patterns reveals limited pathways to seizure end
Authors: Salami Pariya , Borzello Mia , Kramer Mark A. , Westover M. Brandon , Cash Sydney S. 
Published: March 2021

AbstractSeizures result from a variety of pathologies and exhibit great diversity in their dynamics. Although many studies have examined the dynamics of seizure initiation, few have investigated the mechanisms leading to seizure termination. We examined intracranial recordings from patients with intractable focal epilepsy to differentiate seizure termination patterns and investigate whether these termination patterns are indicative of different underlying mechanisms.Seizures (n=710) were recorded intracranially from 104 patients and visually classified as focal or secondarily generalized. Only two patterns emerged from this analysis: (a) those that end simultaneously across the brain (synchronous termination), and (b) those whose ictal activity terminates in some regions but continues in others (asynchronous termination). Finally, seizures ended with either an intermittent bursting pattern (burst suppression pattern), or continuous activity (continuous bursting). These findings allowed for a classification and quantification of the burst suppression ratio, absolute energy and network connectivity of all seizures and comparison across different seizure termination patterns.We found that different termination patterns can manifest within a single patient, even in seizures originating from the same onset locations. Most seizures terminate with patterns of burst suppression regardless of generalization but that seizure that secondarily generalize show burst suppression patterns in 90% of cases, while only 60% of focal seizures exhibit burst suppression. Interestingly, we found similar absolute energy and burst suppression ratios in seizures with synchronous and asynchronous termination, while seizures with continuous bursting were found to be different from seizures with burst suppression, showing lower energy during seizure and lower burst suppression ratio at the start and end of seizure. Finally, network density was observed to increase with seizure progression, with significantly lower densities in seizures with continuous bursting compared to seizures with burst suppression.Our study demonstrates that there are a limited number of seizure termination patterns, suggesting that, unlike seizure initiation, the number of mechanisms underlying seizure termination is constrained. The study of termination patterns may provide useful clues about how these seizures may be managed, which in turn may lead to more targeted modes of therapy for seizure control.
Economic Benefits of COVID-19 Screening Tests with a Vaccine Rollout
Authors: Atkeson Andrew , Droste Michael , Mina Michael J. , Stock James H. 
Published: March 2021

AbstractThis note estimates the costs and benefits of a nationwide COVID-19 screening testing program in the presence of vaccine distribution. Even for an optimistic vaccine rollout scenario, a well-designed federally-funded screening testing program, coupled with self-isolation of those who test positive, pays for itself in terms of increased GDP and is projected to save 20,000 or more lives. The sooner the testing program is put in place, the greater are its net economic benefits. This note updates the December 9, 2020 version to include updated deaths data, later dates for rolling out the screening testing program, and the spread of more contagious variants such as the B.1.1. 7 variant.
Saliva testing is accurate for early-stage and presymptomatic COVID-19
Authors: Johnson Abigail J. , Zhou Shannon , Hoops Suzie L. , Hillmann Benjamin , Schomaker Matthew , Kincaid Robyn , Daniel Jerry , Beckman Kenneth , Gohl Daryl M. , Yohe Sophia , Knights Dan , Nelson Andrew C. 
Published: March 2021

AbstractBackgroundAlthough nasopharyngeal (NP) samples have been considered the gold standard for COVID-19 testing, variability in viral load across different anatomical sites could theoretically cause NP samples to be less sensitive than saliva or nasal samples in certain cases. Self-collected samples also have logistical advantages over NP samples, making them amenable to population-scale screening.MethodsTo evaluate sampling alternatives for population screening, we collected NP, saliva, and nasal samples from two cohorts with varied levels and types of symptoms.ResultsIn a mixed cohort of 60 symptomatic and asymptomatic participants, we found that saliva had 88% concordance with NP when tested in the same testing lab (n = 41), and 68% concordance when tested in different testing labs (n = 19). In a second cohort of 20 participants hospitalized for COVID-19, saliva had 74% concordance with NP tested in the same testing lab, but detected virus in two participants that tested negative with NP on the same day. Medical record review showed that the saliva-based testing sensitivity was related to the timing of symptom onset and disease stage.ConclusionsWe find that no sample site will be perfectly sensitive for COVID-19 testing in all situations, and the significance of negative results will always need to be determined in the context of clinical signs and symptoms. Saliva retained high clinical sensitivity while allowing easier collection, minimizing the exposure of healthcare workers and need for personal protective equipment, and making it a viable option for population-scale testing.
Integrating structured and unstructured citizen science data to improve wildlife population monitoring
Authors: Boersch-Supan Philipp H. , Robinson Robert A. 
Published: March 2021

AbstractAccurate and robust population trend assessments are key to successful biodiversity conservation. Citizen science surveys have provided good evidence of biodiversity declines whilst engaging people with them. Citizen scientists are also collecting opportunistic biodiversity records at unprecedented scales, vastly outnumbering records gathered through structured surveys. Opportunistic records exhibit spatio-temporal biases and heterogeneity in observer effort and skill, but their quantity offers a rich source of information. Data integration, the combination of multiple information sources in a common analytical framework, can potentially improve inferences about populations compared to analysing either in isolation. We combine count data from a structured citizen science survey and detection-nondetection data from an opportunistic citizen science programme. Population trends were modelled using dynamic N-mixture models to integrate both data sources. We applied this approach to two different inferential challenges arising from sparse data: (i) the estimation of population trends for an area smaller than a structured survey stratum, and (ii) the estimation of national population trends for a rare but widespread species. In both cases, data integration yielded population trajectories similar to those estimated from structured survey data alone but had higher precision when the density of opportunistic records was high. In some cases this allowed inferences about population trends where indices derived from single data sources were too uncertain to assess change. However, there were differences in the trend magnitude between the integrated and the standard survey model.We show that data integration of large-scale structured and unstructured data is feasible and offers potential to improve national and regional wildlife trend estimates, although a need to independently validate trends remains. Smaller gains are achieved in areas where uptake of opportunistic recording is low. The integration of opportunistic records from volunteer-selected locations alone may therefore not adequately address monitoring gaps for management and policy applications. To achieve the latter, scheme organisers should consider providing incentives for achieving representative coverage of target areas in both structured and unstructured recording schemes.
Targeting LDHC dysregulates the cell cycle and improves sensitivity to cisplatin and olaparib
Authors: Naik Adviti , Decock Julie 
Published: March 2021

ABSTRACTThe cancer testis antigen (CTA) lactate dehydrogenase C (LDHC) is a promising anti-cancer target with tumor-specific expression, immunogenicity and a role in metabolic reprogramming. Interrogation of the TCGA breast cancer cohort demonstrates upregulation ofLDHCexpression, conferring unfavorable prognosis. Although the role of LDHC is well characterized in spermatocytes, its role in tumors remains largely unknown. We investigated whether LDHC is involved in regulating genomic stability and may be targeted to affect tumor cellular fitness. SilencingLDHCin four breast cancer cell lines significantly increased the presence of giant cells and nuclear aberrations, DNA damage and apoptosis.LDHCsilenced cells demonstrated aberrant cell cycle progression with differential expression of cell cycle checkpoint and DNA damage response regulators. In addition,LDHCsilencing induced microtubule destabilization, culminating in increased mitotic catastrophe and reduced long-term survival. Notably, cisplatin and olaparib treatment further reduced survival ofLDHCsilenced cells. This study supports the therapeutic potential of targeting LDHC to mitigate cancer cell survival, and improve sensitivity to DNA damaging and DNA damage repair inhibiting agents.
CaSR modulates sodium channel-mediated Ca2+-dependent excitability
Authors: Martiszus Briana J. , Tsintsadze Timur , Chang Wenhan , Smith Stephen M. 
Published: March 2021

AbstractIncreasing extracellular [Ca2+] ([Ca2+]o) strongly decreases intrinsic excitability in neurons but the mechanism is unclear. By one hypothesis, [Ca2+]oscreens surface charge reducing voltage-dependent sodium channel (VGSC) activation and by another [Ca2+]oactivates Calcium-sensing receptor (CaSR) closing the sodium-leak channel (NALCN). Here we report that action potential (AP) firing rates increased in wild-type (WT), but not CaSR null mutant (Casr-/-) neocortical neurons, following the switch from physiological to reduced Ca2+-containing Tyrode. However, after membrane potential correction, AP firing increased similarly in both genotypes inconsistent with CaSR regulation of NALCN. Activation of VGSCs was the dominant contributor to the increase in excitability after the [Ca2+]ochange. VGSC conductance-voltage relationships were hyperpolarized by decreasing [Ca2+]ofor Casr-/- neurons indicating CaSR contributes to [Ca2+]o-dependent excitability via VGSCs. Regulation of VGSC gating by [Ca2+]ois the key mechanism mediating [Ca2+]o-dependent changes in neocortical neuron excitability and CaSR influences neuronal excitability by its effects on VGSC gating.
Similarity Measure for Sparse Time Course Data Based on Gaussian Processes
Authors: Liu Zijing , Barahona Mauricio 
Published: March 2021

AbstractWe propose a similarity measure for sparsely sampled time course data in the form of a loglikelihood ratio of Gaussian processes (GP). The proposed GP similarity is similar to a Bayes factor and provides enhanced robustness to noise in sparse time series, such as those found in various biological settings, e.g., gene transcriptomics. We show that the GP measure is equivalent to the Euclidean distance when the noise variance in the GP is negligible compared to the noise variance of the signal. Our numerical experiments on both synthetic and real data show improved performance of the GP similarity when used in conjunction with two distance-based clustering methods.