bluuebunny/crossref_metadata_2025 huggingface dataset:
The virus in the rivers: histories and antibiotic afterlives of the bacteriophage at the sangam in Allahabad
Authors: Kochhar Rijul
Published: July 2020

The confluence (
sangam
) of India's two major rivers, the Ganges and the Yamuna, is located in the city of Allahabad. Ritualistic dips in these river waters are revered for their believed curative power against infections, and salvation from the karmic cycles of birth and rebirth. The sacred and geographic propensities of the rivers have mythic valences in Hinduism and other religious traditions. Yet the connection of these river waters with curativeness also has a base in historical microbiology: near here, the British bacteriologist Ernest Hanbury Hankin, in 1896, first described the ‘bactericidal action of the waters of the Jamuna and Ganges rivers on Cholera microbes’, predating the discovery of bacterial viruses (now known as bacteriophages) by at least two decades. Pursuing the record of these purificatory waters in sacred writings and folklore, and later elaboration in the work of Hankin, this paper traces an epistemology of time that connects the mythic to the post-Hankin modern scientific, asking how imaginations of the waters’ antibacterial properties are articulated through idioms of faith, filth and the phage. The paper explores how the bacteriophage virus comes to be spoken about within secular and sacred epistemes of infection and riverine pollution, among contemporary historians, biologists and doctors, and in the city's museums. At the same time, it traces the phage in histories arcing from the ancient religious literature, to colonial disease control efforts, to today, where bacteriophages are being conceived as a potential response to the crisis of planetary antimicrobial resistance (AMR). Allahabad presents a ‘cosmotechnics’ where faith, filth and phage are inextricably intertwined, generating complex triangulations between natural ecologies, cultural practices and scientific imaginations. Cosmotechnics therefore opens up novel avenues to reimagine the phage as a protean object, one that occupies partial and multiple spaces in the historico-mytho-scientific arena of Allahabad today.
Hawking radiation in optics and beyond
Authors: Aguero-Santacruz Raul , Bermudez David
Published: July 2020

Hawking radiation was originally proposed in astrophysics, but it has been generalized and extended to other physical systems receiving the name of analogue Hawking radiation. In the last two decades, several attempts have been made to measure it in a laboratory, and one of the most successful systems is in optics. Light interacting in a dielectric material causes an analogue Hawking effect, in fact, its stimulated version has already been detected and the search for the spontaneous signal is currently ongoing. We briefly review the general derivation of Hawking radiation, then we focus on the optical analogue and present some novel numerical results. Finally, we call for a generalization of the term Hawking radiation.

This article is part of a discussion meeting issue ‘The next generation of analogue gravity experiments’.
Trapped-ion toolkit for studies of quantum harmonic oscillators under extreme conditions
Authors: Wittemer Matthias , Schröder Jan-Philipp , Hakelberg Frederick , Kiefer Philip , Fey Christian , Schuetzhold Ralf , Warring Ulrich , Schaetz Tobias
Published: July 2020

Many phenomena described in relativistic quantum field theory are inaccessible to direct observations, but analogue processes studied under well-defined laboratory conditions can present an alternative perspective. Recently, we demonstrated an analogy of particle creation using an intrinsically robust motional mode of two trapped atomic ions. Here, we substantially extend our classical control techniques by implementing machine-learning strategies in our platform and, consequently, increase the accessible parameter regime. As a proof of methodology, we present experimental results of multiple quenches and parametric modulation of an unprotected motional mode of a single ion, demonstrating the increased level of real-time control. In combination with previous results, we enable future experiments that may yield entanglement generation using a process in analogy to Hawking radiation.

This article is part of a discussion meeting issue ‘The next generation of analogue gravity experiments’.
Optical analogue gravity physics: resonant radiation
Authors: Petty Jack , König Friedrich
Published: July 2020

The photonic crystal fibre (PCF) is a unique medium giving us the opportunity to perform experiments in carefully chosen regimes with precision and control. Using PCFs, we can perform analogue gravity experiments to study the physics of Hawking radiation and related processes such as resonant radiation. We discuss the similarities and differences between these processes and experimentally investigate the limits of effects of this type, dis- covering a new regime of record efficiency. We measure a 60% energy conversion efficiency from a pump to a visible femtosecond pulse by the process of resonant radiation, and demonstrate its extraordinary tunability in wavelength and bandwidth. Beyond analogue gravity, these femtosecond visible pulses provide a desirable laser source useful across a variety of modern scientific fields.

This article is part of a discussion meeting issue ‘The next generation of analogue gravity experiments’.
Optical analogues of black-hole horizons
Authors: Rosenberg Yuval
Published: July 2020

Hawking radiation is unlikely to be measured from a real black hole, but can be tested in laboratory analogues. It was predicted as a consequence of quantum mechanics and general relativity, but turned out to be more universal. A refractive index perturbation produces an optical analogue of the black-hole horizon and Hawking radiation that is made of light. We discuss the central and recent experiments of the optical analogue, using hands-on physics. We stress the roles of classical fields, negative frequencies, ‘regular optics’ and dispersion. Opportunities and challenges ahead are briefly mentioned.

This article is part of a discussion meeting issue ‘The next generation of analogue gravity experiments’.
Classical hydrodynamics for analogue space–times: open channel flows and thin films
Authors: Rousseaux Germain , Kellay Hamid
Published: July 2020

Here we review the way to build analogue space–times in open channel flows by looking at the flow phase diagram and the corresponding analogue experiments performed during the last years in the associated flow regimes. Thin films like the circular jump with different dispersive properties are discussed with the introduction of a brand new system for the next generation of analogue gravity experiments: flowing soap films with their capillary/elastic waves.

This article is part of a discussion meeting issue ‘The next generation of analogue gravity experiments’.
On the limits of experimental knowledge
Authors: Evans P. W. , Thébault K. P. Y.
Published: July 2020

To demarcate the limits of experimental knowledge, we probe the limits of what might be called an experiment. By appeal to examples of scientific practice from astrophysics and analogue gravity, we demonstrate that the reliability of knowledge regarding certain phenomena gained from an experiment is not circumscribed by the manipulability or accessibility of the target phenomena. Rather, the limits of experimental knowledge are set by the extent to which strategies for what we call ‘inductive triangulation’ are available: that is, the validation of the mode of inductive reasoning involved in the source-target inference via appeal to one or more distinct and independent modes of inductive reasoning. When such strategies are able to partially mitigate reasonable doubt, we can take a theory regarding the phenomena to be well supported by experiment. When such strategies are able to fully mitigate reasonable doubt, we can take a theory regarding the phenomena to be established by experiment. There are good reasons to expect the next generation of analogue experiments to provide genuine knowledge of unmanipulable and inaccessible phenomena such that the relevant theories can be understood as well supported.

This article is part of a discussion meeting issue ‘The next generation of analogue gravity experiments’.
Dynamics landscape for acoustic superradiance
Authors: Gooding Cisco
Published: July 2020

We analyse the behaviour of acoustic vortex beams interacting with rotating, fluid-saturated porous materials. Regions of the parameter space that exhibit distinct dynamical features are identified, with a focus on features that are relevant to the characterization of rotational superradiance. We discuss the similarities and differences between two recent proposals to observe acoustic superradiance with rotating, air-saturated sound absorbers. Finally, theoretical predictions for macroscopic acoustic scattering, obtained by averaging over interactions between the fluid and the porous material at the microscopic level, are compared with predictions of the first-Born approximation.

This article is part of a discussion meeting issue ‘The next generation of analogue gravity experiments’.
Aeromicrobium chenweiae sp. nov. and Aeromicrobium yanjiei sp. nov., isolated from Tibetan antelope (Pantholops hodgsonii) and plateau pika (Ochotona curzoniae), respectively
Authors: Li Junqin , Lei Wenjing , Yang Jing , Lu Shan , Jin Dong , Lai Xin-He , Zhang Sihui , Cheng Yanpeng , Mi Fei , Huang Yuyuan , Pu Ji , Dong Kui , Tian Zhi , Wu Xiaomin , Huang Ying , Wang Suping , Xu Jianguo
Published: July 2020

Four novel strains (592T, S592, MF47T and SMF47) were isolated from Tibetan antelopes (Pantholops hodgsonii) and plateau pikas (Ochotona curzoniae), respectively. The cells were aerobic, non-motile, Gram-stain- and catalase-positive, rod-shaped bacteria. The 16S rRNA gene sequences of the four strains showed highest similarities to

Aeromicrobium fastidiosum

DSM 10552T (98.1, 98.6, 98.7 and 98.7 %, respectively), and the phylogenetic analyses based on 16S rRNA gene and genomic sequences indicated that strains 592T and MF47T represent two novel species. The four isolates produced acid from l-rhamnose, d-xylose and cellobiose, but were unable to reduce nitrate. The DNA G+C contents of strains 592T and MF47T were 70.3 and 69.8 mol%, respectively. The digital DNA–DNA hybridization value between strains 592T and MF47T was 32.6 %, lower than the threshold of 70 %, indicating they belong to different species. The four strains’ genomes displayed less than 24.6 % DNA–DNA relatedness with all available genomes of the genus

Aeromicrobium

in the NCBI database, including

Aeromicrobium fastidiosum

NBRC 14897T and

Aeromicrobium ginsengisoli

JCM 14732T. The major fatty acids of the four strains were C18 : 1
 ω9c and C18 : 0 10-methyl, and the main polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol. The predominant respiratory quinones were MK-9(H4) and MK-8(H4). The cell-wall peptidoglycan contained ll-diaminopimelic acid. Based on these genotypic, phenotypic and biochemical analyses, it is proposed that the four unidentified bacteria be classified as two novel species, Aeromicrobium chenweiae sp. nov. and Aeromicrobium yanjiei sp. nov. The type strains are 592T (=CGMCC1.16526T=DSM 106289T) and MF47T (=CGMCC 1.17444T=JCM 33790T), respectively.
Molecular characterization of a novel bla
CTX-M-3-carrying Tn6741 transposon in Morganella morganii isolated from swine
Authors: Luo Xingwei , Zhai Yajun , He Dandan , Cui Xiaodie , Yang Yingying , Yuan Li , Liu Jianhua , Hu Gongzheng
Published: July 2020

Introduction. The bla
CTX-M-3 gene has rarely been reported in

Morganella morganii

strains and its genetic environment has not yet been investigated.

Aim. To identify the bla
CTX-M-3 gene in

M. morganii

isolated from swine and characterize its genetic environment.

Methodology. A

M. morganii

isolate (named MM1L5) from a deceased swine was identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and subjected to antimicrobial susceptibility testing. The bla genes were detected and then the genetic location and environment of bla
CTX-M-3 were investigated by Southern blot and PCR mapping, respectively. The M. morganii bla
CTX-M-3 gene was cloned and expressed in

Escherichia coli

.

Results. Isolate MM1L5 harboured the bla
CTX-M-3 and bla
TEM-1 genes. The bla
CTX-M-3 gene, located on the chromosome, was co-carried with an IS26 and bla
TEM-1 gene by a novel 6361 bp IS26-flanked composite transposon, designated Tn6741. This transposon consisted of a novel bla
CTX-M-3-containing module, IS26-ΔISEcp1-bla
CTX-M-3-Δorf477-IS26 (named Tn6710), and a bla
TEM-1-containing module, IS26-Δorf477-bla
TEM-1-tnpR-IS26, differing from previous reports. Phylogenetic analysis showed a significant variation based on the sequence of Tn6741, as compared to those of other related transposons. Interestingly, although the cloned bla
CTX-M-3 gene could confer resistance to ceftiofur, cefquinome, ceftriaxone and cefotaxime, one amino acid substitution (Ile-142-Thr) resulted in a significant reduction of resistance to these antimicrobials.

Conclusion. This is the first time that bla
CTX-M-3 has been identified on a chromosome from a

M. morganii

isolate. Furthermore, the bla
CTX-M-3 gene was located with an IS26 element and bla
TEM-1 gene on a novel IS26-flanked composite transposon, Tn6741, suggesting that Tn6741 might act as a reservoir for the bla
CTX-M-3 and bla
TEM-1 genes and may become an important vehicle for their dissemination among

M. morganii

.
A privacy-preserving Bayesian network model for personalised COVID19 risk assessment and contact tracing
Authors: Fenton Norman E , McLachlan Scott , Lucas Peter , Dube Kudakwashe , Hitman Graham A , Osman Magda , Kyrimi Evangelia , Neil Martin
Published: July 2020

Concerns about the practicality and effectiveness of using Contact Tracing Apps (CTA) to reduce the spread of COVID19 have been well documented and, in the UK, led to the abandonment of the NHS CTA shortly after its release in May 2020. One of the key non-technical obstacles to widespread adoption of CTA has been concerns about privacy. We present a causal probabilistic model (a Bayesian network) that provides the basis for a practical CTA solution that does not compromise privacy. Users of the model can provide as much or little personal information as they wish about relevant risk factors, symptoms, and recent social interactions. The model then provides them feedback about the likelihood of the presence of asymptotic, mild or severe COVID19 (past, present and projected). When the model is embedded in a smartphone app, it can be used to detect new outbreaks in a monitored population and identify outbreak locations as early as possible. For this purpose, the only data needed to be centrally collected is the probability the user has COVID19 and the GPS location.
Standardization of Trypanosoma cruzi DNA extraction and purification protocol from samples collected on Whatman 903 filter paper to Chagas disease diagnosis
Authors: Medina LS Jurado , Ballering G , Bisio M , Ojeda RM , Altcheh J
Published: July 2020

Chagas disease (CD) caused by the parasite Trypanosoma cruzi, belongs to the so-called neglected diseases group. In Argentina about 1,500 children are born with congenital Chagas disease per year. The diagnosis of CD in the newborn relies on the ability to detect parasites in the blood by microscopic observation, as the serological tests are ruled out because of the presence of maternal antibodies. CD treatment is more effective during the acute phase of infection. Early diagnosis and treatment of the disease is thus very important. The Argentinian National Program for early detection of metabolic diseases uses Whatman903 filter paper for blood sampling. This type of sample collection presents many advantages as the use of low blood volumes, minimal biological risk, and easy storage and transportation. The objective of the study was to evaluate the conservation efficiency of blood samples on filter paper in order to access good sensitivity on qPCR results for the detection of T. cruzi. To standardize the procedure, negative samples of blood were infected artificially with serial dilutions of trypomastigotes forms of T. cruzi from the TcVI strain obtained by cell culture in Vero cells. Concentrations between 50000 and 5 parasites/mL were prepared and loaded in filter paper for analysis. DNA extraction was conducted by the QIAamp DNA Mini Kit from QIAGEN. For qPCR, a method based on TaqMan technology was used, with a multiplex reaction for quantification of T. cruzi satellite DNA and an internal amplification control (IAC). The detection limit found from our results was 400 parasites/mL, demonstrating that this method could be a reliable option for the diagnosis of congenital CD by the detection of T. cruzi in blood collected in filter paper.
Gender and trust in government modify the association between mental health and stringency of social distancing related public health measures to reduce COVID-19: a global online survey
Authors: O’Hara Lily , Abdul Rahim Hanan F , Shi Zumin
Published: July 2020

Objectives

To investigate the associations between stringency of COVID-19 social distancing policies and mental health outcomes, and the moderating effect of trust in government and gender.

Design and setting

Cross sectional study involving secondary analysis of publicly available data from a global online COVID-19 survey and the Oxford COVID-19 Government Response Tracker.

Participants

106,497 participants from 58 countries.

Main outcome measures

Outcomes were a worries index and a depression index. Predictors were stringency of policies, trust in government, and gender. Multivariable regression was conducted to determine the three-way interaction between the predictor variables for mental health outcomes, adjusting for age, income and education.

Results

The median age of participants (56.4% women) was 37 years (interquartile range 29 to 48 years). Women had higher worries and depression scores than men. 45.4% distrusted the government and 43.8% trusted the government to take care of its citizens. Among those who strongly trusted the government, an increase in the stringency of policies was associated with a significant increase in the worries index. Among men who distrusted the government, an increase in policy stringency was associated with an increase in the depression index but not the worries index. In women that strongly distrusted the government, there was an inversed U-shaped association between policy stringency and both the worries and depression indices.

Conclusion

As the stringency of public health measures increases, so too do depression and worries. The association is moderated by gender and trust in government. For safe and effective public health measures, governments should develop strategies to increase trust in their actions.
Comparative analysis of the molecular mechanism of resistance to vapendavir across a panel of picornavirus species
Authors: Lanko Kristina , Sun Liang , Froeyen Mathy , Leyssen Pieter , Delang Leen , Mirabelli Carmen , Neyts Johan
Published: July 2020

Vapendavir is a rhino/enterovirus inhibitor that targets a hydrophobic pocket in the viral capsid. Drug-resistant variants were selectedin vitro. Mutations in the drug-binding pocket in VP1 (C199R/Y in hRV14; I194F in PV1; M252L and A156T in EV-D68), typical for this class of compounds, were identified. We also observed mutations that are located outside the pocket (K167E in EV-D68 and G149C in hRV2) and that contribute to the resistant phenotype. Remarkably, the G149C substitution made the replication of human rhinovirus 2 dependent on the presence of vapendavir. Our data suggest that vapendavir binding to the capsid of the dependent isolate may be required to stabilize the viral particle and to allow efficient dissemination of the virus. Our results demonstrate that vapendavir-resistant pheno- and genotypes of clinically relevant picornavirus species are more complex than generally believed.
Personalized Input-Output Hidden Markov Models for Disease Progression Modeling
Authors: Severson Kristen A. , Chahine Lana M. , Smolensky Luba , Ng Kenney , Hu Jianying , Ghosh Soumya
Published: July 2020

Disease progression models are important computational tools in healthcare and are used for tasks such as improving disease understanding, informing drug discovery, and aiding in patient management. Although many algorithms for time series modeling exist, healthcare applications face particular challenges such as small datasets, medication effects, disease heterogeneity, and a desire for personalized predictions. In this work, we present a disease progression model that addresses these needs by proposing a probabilistic time-series model that captures individualized disease states, personalized medication effects, disease-state medication effects, or any combination thereof. The model builds on the framework of an input-output hidden Markov model where the parameters are learned using a structured variational approximation. To demonstrate the utility of the algorithm, we apply it to both synthetic and real-world datasets. In the synthetic case, we demonstrate the benefits afforded by the proposed model as compared to standard techniques. In the real-world cases, we use two Parkinson’s disease datasets to show improved predictive performance when ground truth is available and clinically relevant insights that are not revealed via classic Markov models when ground truth is not available.
RISK FACTORS FOR THE DEVELOPMENT OF HOSPITAL-ACQUIRED PEDIATRIC VENOUS THROMBOEMBOLISM: DEALING WITH POTENTIALLY CAUSAL AND CONFOUNDING RISK FACTORS USING DIRECTED ACYCLIC GRAPH (DAG) ANALYSIS
Authors: Campos Leonardo R. , Petroli Maurício , Sztajnzbok Flavio R. , Costa Elaine S. , Brandão Leonardo R. , Land Marcelo G. P.
Published: July 2020

Introduction

Hospital-acquired venous thromboembolism (HA-VTE) in children comprises multiple risk factors that should not be evaluated separately due to collinearity and multiple cause and effect relationships. This is one of the first case-control study of pediatric HA-VTE risk factors using Directed Acyclic Graph (DAG) analysis.

Material and Methods

Retrospective, case-control study with 22 cases of radiologically proved HA-VTE and 76 controls matched by age, sex, unit of admission, and period of hospitalization. Descriptive statistics was used to define distributions of continuous variables, frequencies, and proportions of categorical variables, with a comparison between cases and controls. Due to many potential risk factors of HA-VTE, a directed acyclic graph (DAG) model was created to identify confounding, reduce bias, and increase precision on the analysis. The final model consisted of a DAG-based conditional logistic regression. The study was approved by the Institutional Review Board (CAAE 58056516.0.0000.5264).

Results

In the initial univariable model, the following variables were selected as potential risk factors for HA-VTE: length of stay (LOS, days), ICU admission in the last 30 days, LOS in ICU, infection, central venous catheter (CVC), L-asparaginase, heart failure, liver failure and nephrotic syndrome. The final model (table 1) revealed LOS (OR=1.108, 95%CI=1.024-1.199, p=0.011), L-asparaginase (OR=27.184, 95%CI=1.639-450.982, p=0.021), and nephrotic syndrome (OR=31.481, 95%CI=1.182-838.706, p=0.039) as independent risk factors for HA-VTE.

Conclusion

The DAG-based approach was useful to clarify the influence of confounders and multiple causalities of HA-VTE. Interestingly, CVC placement - a known thrombotic risk factor highlighted in several studies - was considered a confounder, while LOS, L-asparaginase use and nephrotic syndrome were confirmed as risk factors to HA-VTE. Large confidence intervals are related to the sample size, however the results were significant.

Highlights

HA-VTE comprises multiple risk factors that should not be evaluated separately due to collinearity and confounding

Directed Acyclic Graph (DAG) helps to clarify collinearity and confounding related to multiple cause and effect relationships that exist in HA-VTE risk factors

This is a novel study using DAG-based logistic regression to evaluate risk factors for HA-VTE in children

We reported the importance of medical conditions on the genesis of HA-VTE using a DAG-based approach, which makes it possible to clarify the influence of confounders and multiple causalities, such as catheter, a significant risk factor highlighted in several studies
Genetic inhibition of interleukin-6 receptor signaling and Covid-19
Authors: Bovijn Jonas , Lindgren Cecilia M , Holmes Michael V
Published: July 2020

There are few effective therapeutic options for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Early evidence has suggested that IL-6R blockers may confer benefit, particularly in severe coronavirus disease 2019 (Covid-19).

We leveraged large-scale human genetic data to investigate whether IL6-R blockade may confer therapeutic benefit in Covid-19. A genetic instrument consisting of seven genetic variants in or close to IL6R was recently shown to be linked to altered levels of c-reactive protein (CRP), fibrinogen, circulating IL-6 and soluble IL-6R, concordant to known effects of pharmacological IL- 6R blockade. We investigated the effect of these IL6R variants on risk of hospitalization for Covid- 19 and other SARS-CoV-2-related outcomes using data from The Covid-19 Host Genetics Initiative.

The IL6R variants were strongly associated with serum CRP levels in UK Biobank. Meta-analysis of scaled estimates revealed a lower risk of rheumatoid arthritis (OR 0.93 per 0.1 SD lower CRP, 95% CI, 0.90-0.96, P = 9.5 × 10−7), recapitulating this established indication for IL-6R blockers (e.g. tocilizumab and sarilumab). The IL-6R instrument was associated with lower risk of hospitalization for Covid-19 (OR 0.88 per 0.1 SD lower CRP, 95% CI, 0.78-0.99, P = 0.03). We found a consistent association when using a population-based control group (i.e. all non-cases; OR 0.91 per 0.1 SD lower CRP, 95% CI, 0.87-0.96, P = 4.9 × 10−4). Evaluation of further SARS- CoV-2-related outcomes suggested association with risk of SARS-CoV-2 infection, with no evidence of association with Covid-19 complicated by death or requiring respiratory support. We performed several sensitivity analyses to evaluate the robustness of our findings.

Our results serve as genetic evidence for the potential efficacy of IL-6R blockade in Covid-19. Ongoing large-scale RCTs of IL-6R blockers will be instrumental in identifying the settings, including stage of disease, in which these agents may be effective.
SARS-CoV-2 viral load in the upper respiratory tract of children and adults with early acute COVID-19
Authors: Baggio Stéphanie , L’Huillier Arnaud G. , Yerly Sabine , Bellon Mathilde , Wagner Noémie , Rohr Marie , Huttner Angela , Blanchard-Rohner Géraldine , Loevy Natasha , Kaiser Laurent , Jacquerioz Frédérique , Eckerle Isabella
Published: July 2020

The role of children in the transmission of SARS-CoV-2 is unclear. We analysed viral load at the time of diagnosis in 53 children vs. 352 adults with COVID-19 in the first 5 days post symptom onset. No significant differences in SARS-CoV-2 RNA loads were seen between children and adults.
Self-Collected Anterior Nasal and Saliva Specimens versus Healthcare Worker-Collected Nasopharyngeal Swabs for the Molecular Detection of SARS-CoV-2
Authors: Hanson KE , Barker AP , Hillyard DR , Gilmore N , Barrett JW , Orlandi RR , Shakir SM
Published: July 2020

We prospectively compared healthcare worker-collected nasopharyngeal swabs (NPS) to self-collected anterior nasal swabs (ANS) and straight saliva for the diagnosis of COVID-19 in 354 patients. The positive percent agreement between NPS and ANS or saliva was 86.3% (95% CI: 76.7-92.9) and 93.8% (95% CI: 86.0-97.9), respectively. Negative percent agreement was 99.6% (95% CI: 98-100) for NPS vs. ANS and 97.8% (95% CI: 95.3 – 99.2) for NPS vs. saliva. NPS (n=80) and saliva (n=81) detected more cases than ANS (n=70), but no single specimen type detected all SARS-CoV2 infections.
Regional COVID-19 spread despite expected declines: how mitigation is hindered by spatio-temporal variation in local control measures
Authors: Kortessis Nicholas , Simon Margaret W. , Barfield Michael , Glass Gregory , Singer Burton H. , Holt Robert D.
Published: July 2020

Successful public health regimes for COVID-19 push below unity long-term global Rt –the average number of secondary cases caused by an infectious individual. Most assessments use local information. Populations differ in Rt, amongst themselves and over time. We use a SIR model for two populations to make the conceptual point that even if each locality averages Rt < 1, the overall epidemic can still grow, provided these populations have asynchronous variation in transmission, and are coupled by movement of infectious individuals. This emergent effect in pandemic dynamics instantiates “Parrondo’s Paradox,” -- an entity comprised of distinct but interacting units can behave qualitatively differently than each part on its own. For effective COVID-19 disease mitigation strategies, it is critical that infectious individuals moving among locations be identified and quarantined. This does not warrant indiscriminate prevention of movement, but rather rational, targeted testing and national coordination.
Medical Costs of Keeping the US Economy Open During COVID-19
Authors: Chen Jiangzhuo , Vullikanti Anil , Hoops Stefan , Mortveit Henning , Lewis Bryan , Venkatramanan Srinivasan , You Wen , Eubank Stephen , Marathe Madhav , Barrett Chris , Marathe Achla
Published: July 2020

We use an individual based model and national level epidemic simulations to estimate the medical costs of keeping the US economy open during COVID-19 pandemic under different counterfactual scenarios. We model an unmitigated scenario and 12 mitigation scenarios which differ in compliance behavior to social distancing strategies and to the duration of the stay-home order. Under each scenario we estimate the number of people who are likely to get infected and require medical attention, hospitalization, and ventilators. Given the per capita medical cost for each of these health states, we compute the total medical costs for each scenario and show the tradeoffs between deaths, costs, infections, compliance and the duration of stay-home order. We also consider the hospital bed capacity of each Hospital Referral Region (HRR) in the US to estimate the deficit in beds each HRR will likely encounter given the demand for hospital beds. We consider a case where HRRs share hospital beds among the neighboring HRRs during a surge in demand beyond the available beds and the impact it has in controlling additional deaths.
Rapid and sensitive detection of SARS-CoV-2 antibodies by biolayer interferometry
Authors: Dzimianski John V. , Lorig-Roach Nicholas , O’Rourke Sara M. , Alexander David L. , Kimmey Jacqueline M. , DuBois Rebecca M.
Published: July 2020

Serological testing to evaluate antigen-specific antibodies in plasma is generally performed by rapid lateral flow test strips that lack quantitative results or by high complexity immunoassays that are time- and labor-intensive but provide quantitative results. Here, we describe a novel application of biolayer interferometry for the rapid detection of antigen-specific antibody levels in plasma samples, and demonstrate its utility for quantification of SARS-CoV-2 antibodies. Our biolayer interferometry immunosorbent assay (BLI-ISA) utilizes single-use biosensors in an automated “dip-and-read” format, providing real-time optical measurements of antigen loading, plasma antibody binding, and antibody isotype detection. Complete quantitative results are obtained in less than 20 minutes. BLI-ISA meets or exceeds the performance of high complexity methods such as Enzyme-Linked Immunosorbent Assay (ELISA) and Chemiluminescent Immunoassay. Importantly, our method can be immediately implemented on existing BLI platforms for urgent COVID-19 studies, such as serosurveillance and the evaluation of vaccine candidates. In a broader sense, BLI-ISA can be developed as a novel diagnostic platform to evaluate antibodies and other biomolecules in clinical specimens.
UV-C decontamination for N95 emergency reuse: Quantitative dose validation with photochromic indicators
Authors: Su Alison , Grist Samantha M. , Geldert Alisha , Gopal Anjali , Herr Amy E.
Published: July 2020

With COVID-19 N95 respirator shortages, frontline medical personnel are forced to reuse this disposable – but sophisticated – multilayer textile respirator. Widely used for decontamination of nonporous surfaces, UV-C light has germicidal efficacy on porous, non-planar N95 respirators when ≥1.0 J/cm2 dose is applied across all surfaces. Here, we address outstanding limitations of photochromic indicators (qualitative readout and insufficient dynamic range) and introduce a photochromic UV-C dose quantification technique for: (1) design of UV-C treatments and (2) in-process UV-C dose validation. Our methodology establishes that color-changing dosimetry can achieve the necessary accuracy (>90%), uncertainty (<10%), and UV-C specificity (>95%). Furthermore, we adapt consumer electronics for accessible quantitative readout and extend the dynamic range >10× using optical attenuators. In a measurement infeasible with radiometers, we observe striking 20× dose variation over 3D N95 facepieces. By transforming photochromic indicators into quantitative dosimeters, we illuminate critical design considerations for both photochromic indicators and UV-C decontamination.
COVID-19 Case Series at UnityPoint Health St. Luke’s Hospital in Cedar Rapids, IA
Authors: Edwards Dianna , McGrail Daniel
Published: July 2020

A retrospective, descriptive study of all patients tested for SARS-CoV2 on admission for illness to a community hospital in Iowa from 3/21/20 thru 6/14/20 consisted of evaluation as to demographics, presentation and hospital course. Ninety-one patients were SARS-CoV2 PCR+ with 63% being male and a median age of 60. Cardiovascular disease was a significant comorbidity in the PCR+ group. Fever, cough, dyspnea, nausea, emesis, diarrhea, headache and myalgias were significantly more common in that group, as was an elevated CRP, LDH, serum ferritin and transaminases. Overall survival of the COVID-19 patients was 88%, 77% in the critically ill, 59% of those mechanically ventilated and 33% of those requiring new dialysis. Survival was 93% in those not receiving any antivirals. Survival of those treated with hydroxychloroquine-azithromycin was 92%, compared to 86% of those treated with hydroxychloroquine alone. The latter two groups were significantly more ill than the untreated group. A transition from an early intubation strategy to aggressive utilization of high flow nasal cannula and noninvasive ventilation(i.e BiPAP) was successful in freeing up ICU resources.
On the organization of the locomotor CPG: insights from split-belt locomotion and mathematical modeling
Authors: Latash Elizaveta M. , Lecomte Charly , Danner Simon M. , Frigon Alain , Rybak Ilya A. , Molkov Yaroslav I.
Published: July 2020

Rhythmic limb movements during locomotion are controlled by a central pattern generator (CPG) circuits located in the spinal cord. It is considered that these circuits are composed of individual rhythm generators (RGs) for each limb interacting with each other through multiple commissural and long propriospinal circuits. The organization and operation of each RG are not fully understood, and different competing theories exist about interactions between its flexor and extensor components, as well as about left-right commissural interactions between the RGs. The central idea of circuit organization proposed in this study is that with an increase of excitatory input to each RGs (or an increase in locomotor speed) the rhythmogenic mechanism within the RGs changes from “flexor-driven” rhythmicity to a “classical half-center” mechanism. We test this hypothesis using our experimental data on changes in duration of stance and swing phases in the intact and spinal cats walking on the ground or tied-belt treadmills (symmetric conditions) or split-belt treadmills with different left and right belt speeds (asymmetric conditions). We compare these experimental data with the results of mathematical modeling, in which simulated CPG circuits operate in similar symmetric and asymmetric conditions with matching or differing control drives to the left and right RGs. The obtained results support the proposed concept of state-dependent changes in RG operation and specific commissural interactions between the RGs. The performed simulations and mathematical analysis of model operation under different conditions provide new insights into CPG network organization and limb coordination during locomotion.

Key Point Summary

Limb movements during locomotion are controlled by neural circuits located within the spinal cord. These circuits include rhythm generators (RGs) controlling each limb interacting through multiple commissural pathways.

The organization and operation of spinal RGs are not fully understood, and different competing concepts exists. We suggest that the operation of RGs is state-dependent, so that with an increase of external excitation the rhythmogenesis changes from “flexor-driven” oscillations to a “classical half-center” mechanism.

A mathematical model of spinal circuits representing bilaterally-interacting RGs has been developed based on the above suggestion and used to interpret experimental data from intact and spinal cats walking on the ground or tied-belt treadmills (symmetric conditions) as well as on split-belt treadmills with different left and right belt speeds (asymmetric conditions).

The performed simulations and mathematical analysis of the model under different conditions provide new insights into operation of spinal circuits and limb coordination during locomotion.
Untangling the animacy organization of occipitotemporal cortex
Authors: Ritchie J. Brendan , Zeman Astrid A. , Bosmans Joyce , Sun Shuo , Verhaegen Kirsten , Op de Beeck Hans P.
Published: July 2020

Some of the most impressive functional specialization in the human brain is found in occipitotemporal cortex (OTC), where several areas exhibit selectivity for a small number of visual categories, such as faces and bodies, and spatially cluster based on stimulus animacy. Previous studies suggest this animacy organization reflects the representation of an intuitive taxonomic hierarchy, distinct from the presence of face- and body-selective areas in OTC. Using human fMRI, we investigated the independent contribution of these two factors – the face-body division and taxonomic hierarchy – in accounting for the animacy organization of OTC, and whether they might also be reflected in the architecture of several deep neural networks. We found that graded selectivity based on animal resemblance to human faces and bodies masquerades as an apparent animacy continuum, which suggests that taxonomy is not a separate factor underlying the organization of the ventral visual pathway.
Neutralization Assay with SARS-CoV-1 and SARS-CoV-2 Spike Pseudotyped Murine Leukemia Virions
Authors: Zheng Yue , Larragoite Erin T. , Lama Juan , Cisneros Isabel , Delgado Julio C. , Slev Patricia , Rychert Jenna , Innis Emily A. , Williams Elizabeth S.C.P. , Coiras Mayte , Rondina Matthew T. , Spivak Adam M. , Planelles Vicente
Published: July 2020

Antibody neutralization is an important prognostic factor in many viral diseases. To easily and rapidly measure titers of neutralizing antibodies in serum or plasma, we developed pseudovirion particles composed of the spike glycoprotein of SARS-CoV-2 incorporated onto murine leukemia virus capsids and a modified minimal MLV genome encoding firefly luciferase. These pseudovirions provide a practical means of assessing immune responses under laboratory conditions consistent with biocontainment level 2.
A novel approach for assessing hypoperfusion in stroke using spatial independent component analysis of resting-state fMRI
Authors: Hu Jiun-Yiing , Kirilina Evgeniya , Nierhaus Till ,   Dr. rer. medic. Dipl.-Ing.(FH), Ovadia-Caro Smadar , Livne Michelle , Villringer Kersten , Margulies Daniel , Fiebach Jochen B. , Villringer Arno , Khalil Ahmed A.
Published: July 2020

Individualized treatment of acute stroke depends on the timely detection of ischemia and potentially salvageable tissue in the brain. Using functional MRI (fMRI), it is possible to characterize cerebral blood flow from blood-oxygen-level-dependent (BOLD) signals without the administration of exogenous contrast agents. In this study, we applied spatial independent component analysis to resting-state fMRI data of 37 stroke patients scanned within 24 hours of symptom onset, 17 of whom received follow-up scans the next day. Our analysis revealed “Hypoperfusion spatially-Independent Components” (HICs) whose spatial patterns of BOLD signal resembled regions of delayed perfusion depicted by dynamic susceptibility contrast MRI. These HICs were detected even in the presence of excessive patient motion, and disappeared following successful tissue reperfusion. The unique spatial and temporal features of HICs allowed them to be distinguished with high accuracy from other components in a user-independent manner (AUC = 0.95, accuracy = 0.96, sensitivity = 1.00, specificity = 0.96). Our study therefore presents a new, non-invasive method for assessing blood flow in acute stroke that minimizes interpretative subjectivity and is robust to severe patient motion.
Evaluating the Simple Arrhenius Equation for the Temperature Dependence of Complex Developmental Processes
Authors: Crapse Joseph , Pappireddi Nishant , Gupta Meera , Shvartsman Stanislav Y. , Wieschaus Eric , Wühr Martin
Published: July 2020

The famous Arrhenius equation is well motivated to describe the temperature dependence of chemical reactions but has also been used for complicated biological processes. Here, we evaluate how well the simple Arrhenius equation predicts complex multistep biological processes, using frog and fruit fly embryogenesis as two canonical models. We find the Arrhenius equation provides a good approximation for the temperature dependence of embryogenesis, even though individual developmental stages scale differently with temperature. At low and high temperatures, however, we observed significant departures from idealized Arrhenius Law behavior. When we model multistep reactions of idealized chemical networks we are unable to generate comparable deviations from linearity. In contrast, we find the single enzyme GAPDH shows non-linearity in the Arrhenius plot similar to our observations of embryonic development. Thus, we find that complex embryonic development can be well approximated by the simple Arrhenius Law and propose that the observed departure from this law results primarily from non-idealized individual steps rather than the complexity of the system.
The Step-Wise C-Truncation and Transport of ESyt3 to Lipid Droplets Reveals a Mother Primordial Cisterna
Authors: Lalioti Vasiliki , Beznoussenko Galina V. , Mironov Alexander A. , Sandoval Ignacio V.
Published: July 2020

Extended synaptotagmins (E-Syts) are endoplasmic reticulum (ER) proteins consisting of an SMP domain and multiple C2 domains that bind phospholipids and Ca2+. E-Syts create contact junctions between the ER and plasma membrane to facilitate lipid exchange. During adipocyte differentiation, the proteasome-based removal of the C2C domain results in targeting of E-Syt3 to the primordial cisterna, a previously undescribed giant annular organelle that mothers the LDs. Further cleavage causes the E-Syt3 relocation to the surface of LDs. Fragmentation of the primordial cisterna and LD budding into its lumen are early events in the biogenesis of LDs in the 3T3-L1 adipocyte. Electron tomography-based 3D reconstruction of the fragmented primordial cisterna revealed patches of a tightly packed E-Syt3-rich network of varicose tubules in close contact with young LDs. Esyt3 binds avidly phosphatidylethanolamine through its SMP domain, a main component of the LD membrane that fosters LD biogenesis. Repression of E-Syt3 effectively inhibits LD biogenesis and growth.
The impact of commercially available ale and lager yeast strains on the fermentative diversity of beers
Authors: Bonatto Diego
Published: July 2020

Yeasts from the speciesSaccharomyces cerevisiae(ale yeast) andSaccharomyces pastorianus(lager yeast) are the main component of beer fermentation. It is known that different beer categories depend on the use of specific ale or lager strains, where the yeast imprint its distinctive fermentative profile to the beer. Despite this, there are no studies reporting how diverse, rich, and homogeneous the beer categories are in terms of commercially available brewing yeast strains. In this work, the diversity, richness, and evenness of different beer categories and commercial yeast strains available for brewing were evaluated by applying quantitative concepts of ecology analysis in a sample of 121,528 beer recipes. For this purpose, the frequency of ale or lager and dry or liquid yeast formulations usage was accessed and its influence in the fermentation temperature, attenuation profile, and number of recipes for a beer category were analyzed. The results indicated that many beer categories are preferentially fermented with dry yeast strains formulations instead of liquid yeasts, despite considering the high number of available liquid yeast formulations. Moreover, ale dry strains are preferentially used for lager brewing. The preferential use of specific yeast formulations drives the diversity, richness, and evenness of a beer category, showing that many yeast strains are potentially and industrially underexplored.
Functional differentiation in the language network revealed by lesion-symptom mapping
Authors: Matchin William , Basilakos Alexandra , den Ouden Dirk-Bart , Stark Brielle C. , Hickok Gregory , Fridriksson Julius
Published: July 2020

Theories of language organization in the brain commonly posit that different regions underlie distinct linguistic mechanisms. However, such theories have been criticized on the grounds that many neuroimaging studies of language processing find similar effects across regions. Moreover, condition by region interaction effects, which provide the strongest evidence of functional differentiation between regions, have rarely been offered in support of these theories. Here we address this by using lesion-symptom mapping in three large, partially-overlapping groups of aphasia patients with left hemisphere brain damage due to stroke (N=121, N=92, N= 218). We identified multiple measure by region interaction effects, associating damage to the posterior middle temporal gyrus with syntactic comprehension deficits, damage to posterior inferior frontal gyrus with expressive agrammatism, and damage to inferior angular gyrus with semantic category word fluency deficits. Our results are inconsistent with recent hypotheses that regions of the language network are undifferentiated with respect to high-level linguistic processing.