bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetry of Macular Vessel Density in Bilateral Early Open-angle Glaucoma With Unilateral Central 10-2 Visual Field Loss
Authors: Lu Peng , Xiao Hui , Chen Hailiu , Ye Dan , Huang Jingjing
Published: June 2020

Précis:

Glaucomatous eyes without detectable 10-2 visual field loss showed significant macular vessel density loss, especially in inferior quadrant of perifoveal area. Macular vessel density loss spatially corresponded with structural and functional damage.

Purpose:

The purpose of this study was to investigate the characteristics, intereye and intraeye asymmetry of macular vessel density assessed by optical coherence tomography (OCT) angiography in bilateral early open-angle glaucoma with unilateral 10-2 visual field loss.

Materials and Methods:

Thirty-two eyes of 16 patients with bilateral early open-angle glaucoma and unilateral 10-2 visual field loss, and 13 eyes of 13 healthy participants were consecutively enrolled. All subjects underwent 30-2, 10-2 visual fields, OCT, and OCT angiography examinations. Intereye differences were compared between the perimetrically affected eye and the unaffected eye in the same patient. Intraeye differences were compared between the affected hemifields and the unaffected hemifields in the same eye with single-hemifield 10-2 visual field loss.

Results:

Macular whole image vessel density of the perimetrically unaffected eyes was lower than the healthy eyes (46.6% vs. 51.1%; P<0.001). Parafoveal vessel density parameters of the perimetrically affected eyes were comparable to the unaffected eyes (all P>0.05). Although inferior perifoveal vessel density of the perimetrically affected eyes was significantly lower than the unaffected eyes (42.2% vs. 46.2%; P=0.007), similar results were found in macular ganglion cell complex. In glaucomatous eyes with single-hemifield loss, perifoveal vessel density and macular ganglion cell complex of the affected hemifields were significantly worse than the unaffected hemifields (43.6% vs. 47.0%, 78.4 μm vs. 89.0 μm; P=0.023 and 0.005; respectively).

Conclusions:

Significant macular microvascular damage was present in glaucomatous eyes without detectable 10-2 visual field damage. The damage of inferior perifoveal vessel density was more significant in early glaucoma. Macular microvascular damage spatially corresponded with functional and structural damage.
The Relationship Between Corneal Hysteresis and Progression of Glaucoma After Trabeculectomy
Authors: Fujino Yuri , Murata Hiroshi , Matsuura Masato , Nakakura Shunsuke , Shoji Nobuyuki , Nakao Yoshitaka , Kiuchi Yoshiaki , Asaoka Ryo
Published: June 2020

Purpose:

The purpose of this study was to investigate the association of corneal hysteresis (CH) measured with Ocular Response Analyzer on the progression of glaucoma after trabeculectomy.

Materials and Methods:

Twenty-four eyes of 19 patients with primary open-angle glaucoma underwent trabeculectomy. A series of visual fields (Humphery Field Analyzer 24-2 SITA-standard) were measured starting after 6 months after trabeculectomy (4.2±5.0 y, mean±SD). The mean total deviation (mTD) of the 52 test points were calculated. In addition, the mTD was divided into the following areas: central area (within central 10 degrees), superior area and inferior area: mTDcentre, mTDsuperior, and mTDinferior, respectively. The relationship between each area’s progression rate of mTD and the 7 variables of baseline age, central corneal thickness, baseline mTD, mean intraocular pressure (IOP), SD of IOP divided by the mean IOP, the difference between baseline IOP obtained before the initiation of any treatment, mean IOP, and CH were analyzed using the linear mixed model, and the optimal model was selected using the model selection method with the second ordered Akaike Information Criterion.

Results:

In the optimal model for mTD progression rate, only CH was selected with the coefficient of 0.11. The optimal model for the mTDcentre progression rate included mean IOP with the coefficient of −0.043 and CH with the coefficient of 0.12, and that for mTDinferior included only CH with the coefficient of 0.089. There was no variable selected in the optimal model for the mTDsuperior progression rate.

Conclusion:

CH is a useful measure in the management of glaucoma after trabeculectomy.
The Limited Sensitivity of Chest Computed Tomography Relative to Reverse Transcription Polymerase Chain Reaction for Severe Acute Respiratory Syndrome Coronavirus-2 Infection
Authors: Waller Joseph V. , Allen Isabel E. , Lin Keldon K. , Diaz Michael J. , Henry Travis S. , Hope Michael D.
Published: June 2020

Objectives

Several studies suggest the sensitivity of chest computed tomography (CT) is far greater than that of reverse transcription polymerase chain reaction (RT-PCR) in diagnosing COVID-19 patients, and therefore, CT should be included as a primary diagnostic tool. This systematic review aims to stratify studies as high or low risk of bias to determine the true sensitivity of CT for severe acute respiratory syndrome coronavirus-2 infection according to the unbiased (low risk) studies, a topic of particular importance given the insufficient quantity of RT-PCR kits in many countries. We focus on sensitivity as that is the chief advantage perceived of CT.

Materials and Methods

This systematic review involved searching the PubMed and Google Scholar databases for articles conducted and published between January 1 and April 15, 2020. The quality assessment tool QUADAS-2 was used to stratify studies according to their risk of bias, and exclusion criteria included not providing the information deemed relevant for such a stratification, such as not indicating if the patients were symptomatic or asymptomatic, or identifying the source of the specimen for the reference standard, RT-PCR (eg, nasal, oropharyngeal, etc). Sensitivity values were then extracted, and random effects meta-analyses were performed.

Results

Of 641 search results, 37 studies (n = 9610 patients) were included in the analysis. The mean sensitivity of RT-PCR for COVID-19 reported by the biased studies was 70% (n = 5409/7 studies; 95% confidence interval [CI], 43–97; I
2 = 99.1%), compared with 78% by unbiased studies (n = 534/4 studies; 95% CI, 69–87, I
2 = 89.9%). For chest CT, the mean sensitivity reported by biased studies was 94% (n = 3371 patients/24 studies; 95% CI, 92–96; I
2 = 93.1%), compared with 75% by unbiased studies (n = 957/10 studies; 95% CI, 67–83; I
2 = 89.5%).

Conclusions

The difference between the sensitivities of CT and RT-PCR for severe acute respiratory syndrome coronavirus-2 infection is lower than previously thought, as after stratifying the studies, the true sensitivity for CT based on the unbiased studies is limited.
Prevalence of Burnout Among Cardiothoracic Radiologists
Authors: Eisenberg Ronald L. , Sotman Timothy E. , Czum Julianna M. , Montner Steven M. , Meyer Cristopher A.
Published: June 2020

Purpose:

Burnout is a psychological syndrome in response to chronic occupational stressors. The prevalence of burnout among medical professionals has been increasing, and recent studies have shown that radiologists are among those affected. We investigated the prevalence of burnout and assessed associated factors among cardiothoracic radiologists.

Materials and Methods:

Society of Thoracic Radiology members were invited to complete an anonymous cross-sectional survey that included an adapted Maslach Burnout Inventory and questions about demographics, work place characteristics, and stressors.

Results:

The survey response rate was 33.1% (290/874). Per-item response rate ranged from 94% to 100% with a median of 99%. The prevalence of emotional exhaustion was 66.8% (186/283), depersonalization was 79% (223/283), and low personal accomplishment was 23% (65/280). There were no statistically significant differences between academic and private practice. There was a trend toward worse burnout in women, but this was not statistically significant. Being in early career (0 to 10 y since fellowship) was associated with low personal accomplishment [odds ratio (OR): 2.07, 95% confidence interval (CI): 1.08-3.99]. Those working fewer than 51 hours per week were significantly less likely to report emotional exhaustion (OR: 0.55, 95% CI: 0.33-0.90). The odds of emotional exhaustion for those producing fewer than 7500 work relative value units per year were approximately half of those exceeding that number (OR: 0.46, 95% CI: 0.22-0.95).

Conclusions:

The prevalence of burnout among cardiothoracic radiologists is comparable to that reported for radiologists in other subspecialties such as musculoskeletal and interventional radiology. High work relative value unit productivity and longer work hours are associated with higher prevalence of burnout.
Time-aggregated mobile phone mobility data are sufficient for modelling influenza spread: the case of Bangladesh
Authors: Engebretsen Solveig , Engø-Monsen Kenth , Aleem Mohammad Abdul , Gurley Emily Suzanne , Frigessi Arnoldo , de Blasio Birgitte Freiesleben
Published: June 2020

Human mobility plays a major role in the spatial dissemination of infectious diseases. We develop a spatio-temporal stochastic model for influenza-like disease spread based on estimates of human mobility. The model is informed by mobile phone mobility data collected in Bangladesh. We compare predictions of models informed by daily mobility data (reference) with that of models informed by time-averaged mobility data, and mobility model approximations. We find that the gravity model overestimates the spatial synchrony, while the radiation model underestimates the spatial synchrony. Using time-averaged mobility resulted in spatial spreading patterns comparable to the daily mobility model. We fit the model to 2014–2017 influenza data from sentinel hospitals in Bangladesh, using a sequential version of approximate Bayesian computation. We find a good agreement between our estimated model and the case data. We estimate transmissibility and regional spread of influenza in Bangladesh, which are useful for policy planning. Time-averaged mobility appears to be a good proxy for human mobility when modelling infectious diseases. This motivates a more general use of the time-averaged mobility, with important implications for future studies and outbreak control. Moreover, time-averaged mobility is subject to less privacy concerns than daily mobility, containing less temporal information on individual movements.
The Bayesian superorganism: externalized memories facilitate distributed sampling
Authors: Hunt Edmund R. , Franks Nigel R. , Baddeley Roland J.
Published: June 2020

A key challenge for any animal (or sampling technique) is to avoid wasting time by searching for resources (information) in places already found to be unprofitable. In biology, this challenge is particularly strong when the organism is a central place forager—returning to a nest between foraging bouts—because it is destined repeatedly to cover much the same ground. This problem will be particularly acute if many individuals forage from the same central place, as in social insects such as the ants. Foraging (sampling) performance may be greatly enhanced by coordinating movement trajectories such that each ant (walker) visits separate parts of the surrounding (unknown) space. We find experimental evidence for an externalized spatial memory in
Temnothorax albipennis
ants: chemical markers (either pheromones or cues such as cuticular hydrocarbon footprints) that are used by nest-mates to mark explored space. We show these markers could be used by the ants to scout the space surrounding their nest more efficiently through indirect coordination. We also develop a simple model of this marking behaviour that can be applied in the context of Markov chain Monte Carlo methods (Baddeley
et al
. 2019
J. R. Soc. Interface
16
, 20190162 (
doi:10.1098/rsif.2019.0162
)). This substantially enhances the performance of standard methods like the Metropolis–Hastings algorithm in sampling from sparse probability distributions (such as those confronted by the ants) with only a little additional computational cost. Our Bayesian framework for superorganismal behaviour motivates the evolution of exploratory mechanisms such as trail marking in terms of enhanced collective information processing.
SVEP1, a novel human coronary artery disease locus, promotes atherosclerosis
Authors: Jung In-Hyuk , Elenbaas Jared S. , Alisio Arturo , Santana Katherine , Young Erica P. , Kang Chul Joo , Kachroo Puja , Lavine Kory J. , Razani Babak , Mecham Robert P. , Stitziel Nathan O.
Published: June 2020

A low-frequency variant of SVEP1, an extracellular matrix protein, is associated with risk of coronary disease in humans independent of plasma lipids. Despite a robust statistical association, however, it was unclear if and how SVEP1 might contribute to atherosclerosis. Here, using Mendelian randomization and complementary mouse models, we provide evidence that SVEP1 promotes atherosclerosis in humans and mice. We find that SVEP1 is expressed by vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque. VSMCs also interact with SVEP1, causing proliferation and dysregulation of key differentiation pathways, including integrin and Notch signaling. Fibroblast growth factor receptor transcription increases in VSMCs interacting with SVEP1, and is further increased by the coronary disease-associated SVEP1 variant. These effects ultimately drive inflammation and promote atherosclerosis. Taken together, our results suggest that VSMC-derived SVEP1 is a pro-atherogenic factor, and support the concept that pharmacological inhibition of SVEP1 should protect against atherosclerosis in humans.
Array-based analysis of SARS-CoV-2, other coronaviruses, and influenza antibodies in convalescent COVID-19 patients
Authors: Steiner Daniel J. , Cognetti John S. , Luta Ethan P. , Klose Alanna M. , Bucukovski Joseph , Bryan Michael R. , Schmuke Jon J. , Nguyen-Contant Phuong , Sangster Mark Y. , Topham David J. , Miller Benjamin L.
Published: June 2020

Detection of antibodies to upper respiratory pathogens is critical to surveillance, assessment of the immune status of individuals, vaccine development, and basic biology. The urgent need for antibody detection tools has proven particularly acute in the COVID-19 era. We report a multiplex label-free antigen microarray on the Arrayed Imaging Reflectometry (AIR) platform for detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43) and three strains of influenza. We find that the array is readily able to distinguish uninfected from convalescent COVID-19 subjects, and provides quantitative information about total Ig, as well as IgG- and IgM-specific responses.
Epithelial Tissues as Active Solids: From Nonlinear Contraction Pulses to Rupture Resistance
Authors: Armon Shahaf , Bull Matthew S. , Moriel Avraham , Aharoni Hillel , Prakash Manu
Published: June 2020

Epithelial tissues in many contexts can be viewed as soft active solids. Their active nature is manifested in the ability of individual cells within the tissue to contract and/or remodel their mechanical properties in response to various conditions. Little is known about the emergent properties of such materials. Specifically, how an individual cellular activity gives rise to collective spatiotemporal patterns is not fully understood. Recently we reported the observation of ultrafast contraction pulses in the dorsal epithelium ofT.adhaerensin vivo [1] and speculated these propagate via mechanical fields. Other accumulating evidence suggest mechanics is involved in similar contractile patterns in embryonic development in vivo and in cellular monolayers in vitro. Here we show that a widespread cellular response – activation of contraction in response to stretch – is sufficient to give rise to nonlinear propagating contraction pulses. Using a minimal numerical model and theoretical considerations we show how such mechanical pulses emerge and propagate, spontaneously or in response to external stretch. The model – whose mathematical structure resembles that of reaction-diffusion systems – explains observed phenomena inT. adhaerens(e.g. excitable or spontaneous pulses, pulse interaction) and predicts other phenomena (e.g. symmetric strain profile, “spike trains”). Finally, we show that in response to external tension, such an active two-dimensional sheet lowers and dynamically distributes the strains across its surface, hence facilitating tissue resistance to rupture. Adding a cellular softening-threshold further enhances the tissue resistance to rupture at cell-cell junctions. As cohesion is at the heart of epithelial physiology, our model may be relevant to many other epithelial systems, even if manifested at different time/length scales.

Significance

Our work demonstrates that many observed dynamical phenomena in epithelial tissues can be explained merely by mechanical cell-cell interactions, and do not require chemical diffusion or transport between cells (though chemical activity may participate in relevant intracellular processes). Specifically, we show that single cell extension-induced-contraction (EIC) is sufficient to generate propagating contraction pulses, which also increase the tissue’s resistance to rupture, an essential function of epithelia. Our results may shed light on how epithelial tissues function under challenging physiological conditions, e.g. in lung, gut, vasculature and other biomedical contexts. Our results may also be relevant in the study of early evolution of multicellularity and the nervous-muscular systems. Finally, the work offers guidelines for designing soft synthetic solids with improved mechanical properties.
Thein vitroantiviral activity of the anti-hepatitis C virus (HCV) drugs daclatasvir and sofosbuvir against SARS-CoV-2
Authors: Sacramento Carolina Q. , Fintelman-Rodrigues Natalia , Temerozo Jairo R. , de Paula Dias Da Silva Aline , da Silva Gomes Dias Suelen , dos Santos da Silva Carine , Ferreira André C. , Mattos Mayara , Pão Camila R. R. , de Freitas Caroline S. , Soares Vinicius Cardoso , Hoelz Lucas Villas Bôas , Fernandes Tácio Vinício Amorim , Branco Frederico Silva Castelo , Bastos Mônica Macedo , Boechat Núbia , Saraiva Felipe B. , Ferreira Marcelo Alves , Rajoli Rajith K. R. , Pedrosa Carolina S. G. , Vitória Gabriela , Souza Letícia R. Q. , Goto-Silva Livia , Guimarães Marilia Zaluar , Rehen Stevens K. , Owen Andrew , Bozza Fernando A. , Bou-Habib Dumith Chequer , Bozza Patrícia T. , Souza Thiago Moreno L.
Published: June 2020

Current approaches of drugs repurposing against 2019 coronavirus disease (COVID-19) have not proven overwhelmingly successful and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to cause major global mortality. Daclatasvir (DCV) and sofosbuvir (SFV) are clinically approved against hepatitis C virus (HCV), with satisfactory safety profile. DCV and SFV target the HCV enzymes NS5A and NS5B, respectively. NS5A is endowed with pleotropic activities, which overlap with several proteins from SARS-CoV-2. HCV NS5B and SARS-CoV-2 nsp12 are RNA polymerases that share homology in the nucleotide uptake channel. We thus tested whether SARS-COV-2 would be susceptible these anti-HCV drugs. DCV consistently inhibited the production of infectious SARS-CoV-2 in Vero cells, in the hepatoma cell line (HuH-7) and in type II pneumocytes (Calu-3), with potencies of 0.8, 0.6 and 1.1 μM, respectively. Although less potent than DCV, SFV and its nucleoside metabolite inhibited replication in Calu-3 cells. Moreover, SFV/DCV combination (1:0.15 ratio) inhibited SARS-CoV-2 with EC50of 0.7:0.1 μM in Calu-3 cells. SFV and DCV prevented virus-induced neuronal apoptosis and release of cytokine storm-related inflammatory mediators, respectively. Both drugs inhibited independent events during RNA synthesis and this was particularly the case for DCV, which also targeted secondary RNA structures in the SARS-CoV-2 genome. Concentrations required for partial DCVin vitroactivity are achieved in plasma at Cmax after administration of the approved dose to humans. Doses higher than those approved may ultimately be required, but these data provide a basis to further explore these agents as COVID-19 antiviral candidates.
Negative density-dependent parasitism in a group-living carnivore
Authors: Albery Gregory F , Newman Chris , Ross Julius Bright , Bansal Shweta , Buesching Christina
Published: June 2020

Animals living at high population densities commonly experience greater exposure to disease, leading to increased parasite burdens. However, social animals can benefit immunologically and hygienically from cooperation, and individuals may alter their socio-spatial behaviour in response to infection, both of which could counteract density-related increases in exposure. Consequently, the costs and benefits of sociality for disease are often uncertain. Here, we use a long-term study of a wild European badger population (Meles meles) to investigate how within-population variation in host density determines infection with multiple parasites. Four out of five parasite taxa exhibited consistent spatial hotspots of infection, which peaked among badgers living in areas of low local population density. Combined movement, survival, spatial, and social network analyses revealed that parasite avoidance was the likely cause of this negative density dependence, with possible roles for localised mortality, encounter-dilution effects, and micronutrient-enhanced immunity. These findings demonstrate that animals can organise their societies in space to minimise parasite infection, with important implications for badger behavioural ecology and for the control of badger-associated diseases.
The Italian National Surveillance System for Occupational Injuries: Conceptual Framework and Fatal Outcomes, 2002–2016
Authors: Campo G , Cegolon L , De Merich D , Fedeli U , Pellicci M , Pavanello S , Guglielmi A , Mastrangelo G
Published: June 2020

Background

A national database of work related injuries was established in Italy since 2002, collecting information on the injured person, his/her work tasks, the workplace as well as risk factors contributing to accident dynamics, according to a model called Infor.Mo.

Methods

The present is a qualitative description of occupational fatal injuries, excluding work-related fatal traffic injuries, that occurred in Italy from 2002 to 2016 (15 years).

Results

4,874 victims were registered, all were males, mainly of >51 years of age (50.5%), predominantly self-employed (27.8%) or workers with non-standard contracts (25%). About 18.4% and 17.3% of fatal accidents occurred in micro-enterprises belonging to, respectively, Construction and Agriculture. A wide range of nationalities (59 countries in addition to Italy) was identified. 18.9% work related fatal injuries were due to some form of dangerous energy □ mechanical, thermal, electrical, chemical □ freely present in the workplace. Fall of workers from height (33.5%), heavy bodies falling on workers from height (16.7%) and vehicles exiting their route and overturning (15.9%) were the accidents causing the greatest proportion of occupational fatal injuries. The activity of the injured person made up 43.3% of 9,386 risk factors identified in 4,874 fatalities. Less common risk factors were related to: work equipment (20.2%); work environment (14.9%); the activity of third parties (9.8%); personal protective equipment/clothing (8.0%) and materials (3.7%). The activity of the injured person remained the most relevant contributing factor even when the accident was caused by two or more risk factors.

Discussion

Occupational fatal injuries occurred mainly in small size firms. Small companies generally have less resources to catch up with the continuously evolving health and safety at work regulations; moreover, they tend to be less compliant with occupational health and safety regulations since are less likely to be inspected by occupational vigilance services. As a result, the enforcement of regulations to control the occupational risk factors of occupational injuries is seemingly costly and scarcely effective. An alternative approach that is being introduced in Italy relies on the use of economic incentives to promote safe and healthy workplaces.
National Early Warning Scores and COVID-19 deaths in care homes: a longitudinal ecological study
Authors: Stow Daniel , Barker Robert O , Matthews Fiona E , Hanratty Barbara
Published: June 2020

Objectives

To investigate whether patterns of National Early Warning Scores (NEWS/NEWS2) in care homes during the COVID pandemic correspond with area-level COVID-19 death registrations from care homes.

Study design

Longitudinal ecological study.

Setting

460 Care home units using the same software package to collect data on residents, from 46 local authority areas in England.

Participants

6,464 care home residents with at least one NEWS recording.

Exposure measure

29,656 anonymised person-level NEWS from 29/12/2019 to 20/05/2020 with component physiological measures: systolic blood pressure, respiratory rate, pulse rate, temperature, and oxygen saturation. Baseline values for each measure calculated using 80th and 20th centile scores before March 2020.

Outcome measure

Time series comparison with Office for National Statistics (ONS) weekly reported registered deaths of care home residents where COVID-19 was the underlying cause of death, and all other deaths (excluding COVID-19) up to 10/05/2020.

Results

Deaths due to COVID-19 were registered from 23/03/2020 in the study geographical areas. Between 23/03/2020 and 10/05/2020, there were 5,753 deaths (1,532 involving COVID-19 and 4,221 other causes). The proportion of above-baseline NEWS increased from 16/03/2020 and closely followed the rise and fall in COVID-19 deaths over the study period. The proportion of above-baseline oxygen saturation, respiratory rate and temperature measurements also increased approximately two weeks before peaks in care home deaths in corresponding geographical areas.

Conclusions

NEWS may make a useful contribution to disease surveillance in care homes during the COVID-19 pandemic. Oxygen saturation, respiratory rate and temperature could be prioritised as they appear to signal rise in mortality almost as well as total NEWS. This study reinforces the need to collate data from care homes, to monitor and protect residents’ health. Further work using individual level outcome data is needed to evaluate the role of NEWS in the early detection of resident illness.
Prothrombotic antiphospholipid antibodies in COVID-19
Authors: Zuo Yu , Estes Shanea K. , Ali Ramadan A. , Gandhi Alex A. , Yalavarthi Srilakshmi , Shi Hui , Sule Gautam , Gockman Kelsey , Madison Jacqueline A. , Zuo Melanie , Yadav Vinita , Wang Jintao , Woodward Wrenn , Lezak Sean P. , Lugogo Njira L. , Smith Stephanie A. , Morrissey James H. , Kanthi Yogendra , Knight Jason S.
Published: June 2020

Patients with coronavirus disease 19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. At the same time, lung histopathology often reveals fibrin-based occlusion in the small vessels of patients who succumb to the disease. Antiphospholipid syndrome (APS) is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies (aPL) targeting phospholipids and phospholipid-binding proteins. Case series have recently detected aPL in patients with COVID-19. Here, we measured eight types of aPL [anticardiolipin IgG/IgM/IgA, anti-beta-2 glycoprotein I IgG/IgM/IgA, and anti-phosphatidylserine/prothrombin (aPS/PT) IgG/IgM] in the sera of 172 patients hospitalized with COVID-19. We detected aPS/PT IgG in 24%, anticardiolipin IgM in 23%, and aPS/PT IgM in 18%. Any aPL was present in 52% of patients using the manufacturer’s threshold and in 30% using a more stringent cutoff (≥40 units). Higher levels of aPL were associated with neutrophil hyperactivity (including the release of neutrophil extracellular traps/NETs), higher platelet count, more severe respiratory disease, and lower glomerular filtration rate. Similar to patients with longstanding APS, IgG fractions isolated from patients with COVID-19 promoted NET release from control neutrophils. Furthermore, injection of these COVID-19 IgG fractions into mice accelerated venous thrombosis. Taken together, these studies suggest that a significant percentage of patients with COVID-19 become at least transiently positive for aPL and that these aPL are potentially pathogenic.
Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR
Authors: Lu Jing , Peng Jinju , Xiong Qianling , Liu Zhe , Lin Huifang , Tan Xiaohua , Kang Min , Yuan Runyu , Zeng Lilian , Zhou Pingping , Liang Chumin , Yi Lina , Plessis Louis du , Song Tie , Ma Wenjun , Sun Jiufeng , Pybus Oliver G , Ke Changwen
Published: June 2020

Background

COVID-19 pandemic is underway. Some COVID-19 cases re-tested positive for SARS-CoV-2 RNA after discharge raising the public concern on their infectivity. Characterization of re-positive cases are urgently needed for designing intervention strategies.

Methods

Clinical data were obtained through Guangdong COVID-19 surveillance network. Neutralization antibody titre was determined using a microneutralization assay. Potential infectivity of clinical samples was evaluated after the cell inoculation. SARS-CoV-2 RNA was detected using three different RT-PCR kits and multiplex PCR with nanopore sequencing.

Results

Among 619 discharged COVID-19 cases, 87 were re-tested as SARS-CoV-2 positive in circumstance of social isolation. All re-positive cases had mild or moderate symptoms in initial diagnosis and a younger age distribution (mean, 30.4). Re-positive cases (n=59) exhibited similar neutralization antibodies (NAbs) titre distributions to other COVID-19 cases (n=150) parallel-tested in this study. No infective viral strain could be obtained by culture and none full-length viral genomes could be sequenced for all re-positive cases.

Conclusions

Re-positive SARS-CoV-2 was not caused by the secondary infection and was identified in around 14% of discharged cases. A robust Nabs response and a potential virus genome degradation were detected from nearly all re-positive cases suggesting a lower transmission risk, especially through a respiratory route.
Can the protection be among us? Previous viral contacts and prevalent HLA alleles avoiding an even more disseminated COVID-19 pandemic
Authors: Antonio Eduardo Cheuiche , Meireles Mariana Rost , de Souza Bragatte Marcelo Alves , Vieira Gustavo Fioravanti
Published: June 2020

COVID-19 is bringing scenes of sci-fi movies into real life, and it seems to be far from over. Infected individuals exhibit variable severity, suggesting the involvement of the genetic constitution of populations and previous cross-reactive immune contacts in the individuals’ disease outcome. To investigate the participation of MHC alleles in COVID-19 severity, the combined use of HLA-B*07, HLA-B*44, HLA-DRB1*03, and HLA-DRB1*04 grouped affected countries presenting similar death rates, based only on their allele frequencies. To prospect T cell targets in SARS-CoV-2, we modeled 3D structures of HLA-A*02:01 complexed with immunogenic epitopes from SAR-CoV-1 and compared them with models containing the corresponding SARS-CoV-2 peptides. It reveals molecular conservation between SARS-CoV peptides, evidencing that the corresponding current sequences are putative T cell epitopes. These structures were also compared with other HCoVs sequences, and with a panel of epitopes from unrelated viruses, looking for the triggers of cross-protection in asymptomatic and uninfected individuals. 229E, OC43, and impressively, viruses involved in endemic human infections share fingerprints of immunogenicity with SARS-CoV peptides. Wide-scale HLA genotyping in COVID-19 patients shall improve prognosis prediction. Structural identification of previous triggers paves the way for herd immunity examination and wide spectrum vaccine development.
Lattice Model of Mitigated Epidemic
Authors: Garanin Dmitry A. , Chudnovsky Eugene M.
Published: June 2020

We study a statistical lattice model of a mitigated epidemic. The level of mitigation, defined by measures to slow down the spread of the infection, is characterized by the infection transmissivity. It is determined by people’s mobility, frequency of contacts, and probability to catch the virus from a contact. In the absence of testing the infected people are isolated for a finite period of time during which they are symptomatic. In the presence of testing, people become isolated a soon as they are tested positive. We compute time dependence of daily new infections as function of transmissivity, initial infection, and testing. The duration of the epidemic increases rapidly with the increased level of mitigation while the number of people falling sick daily decreases. Testing, regardless of the level, has little effect on the duration of the epidemic. The total number of people who contract the disease over the lifetime of the epidemic depends weakly on its duration. It does not change significantly for the homogeneous testing of the population at the level below 10% daily.
SARS-CoV-2 Community Transmission During Shelter-in-Place in San Francisco
Authors: Chamie Gabriel , Marquez Carina , Crawford Emily , Peng James , Petersen Maya , Schwab Daniel , Schwab Joshua , Martinez Jackie , Jones Diane , Black Douglas , Gandhi Monica , Kerkhoff Andrew D. , Jain Vivek , Sergi Francesco , Jacobo Jon , Rojas Susana , Tulier-Laiwa Valerie , Gallardo-Brown Tracy , Appa Ayesha , Chiu Charles , Rodgers Mary , Hackett John ,   CLIAhub Consortium, Kistler Amy , Hao Samantha , Kamm Jack , Dynerman David , Batson Joshua , Greenhouse Bryan , DeRisi Joe , Havlir Diane V.
Published: June 2020

Background

We characterized SARS-CoV-2 infections in a densely-populated, majority Latinx San Francisco community six-weeks into the city’s shelter-in-place order.

Methods

We offered SARS-CoV-2 reverse transcription-PCR and antibody (Abbott ARCHITECT IgG) testing, regardless of symptoms, to all residents (>4 years) and workers in a San Francisco census tract (population: 5,174) at outdoor, community-mobilized events over four days. We estimated SARS-CoV-2 point prevalence (PCR-positive) and cumulative incidence (antibody or PCR-positive) in the census tract and evaluated risk factors for recent (PCR-positive/antibody-negative) versus prior infection (antibody-positive/PCR-negative). SARS-CoV-2 genome recovery and phylogenetics were used to measure viral strain diversity, establish viral lineages present, and estimate number of introductions.

Results

We tested 3,953 persons: 40% Latinx; 41% White; 9% Asian/Pacific Islander; and 2% Black. Overall, 2.1% (83/3,871) tested PCR-positive: 95% were Latinx and 52% asymptomatic when tested. 1.7% of residents and 6.0% of workers (non-census tract residents) were PCR-positive. Among 2,598 census tract residents, estimated point prevalence of PCR-positives was 2.3% (95%CI: 1.2-3.8%): 3.9% (95%CI: 2.0-6.4%) among Latinx vs. 0.2% (95%CI: 0.0-0.4%) among non-Latinx persons. Estimated cumulative incidence among residents was 6.1% (95%CI: 4.0-8.6%). Prior infections were 67% Latinx, 16% White, and 17% other ethnicities. Among recent infections, 96% were Latinx. Risk factors for recent infection were Latinx ethnicity, inability to shelter-in-place and maintain income, frontline service work, unemployment, and household income <$50,000/year. Five SARS-CoV-2 phylogenetic lineages were detected.

Conclusion

SARS-CoV-2 infections from diverse lineages continued circulating among low-income, Latinx persons unable to work from home and maintain income during San Francisco’s shelter-in-place ordinance.
Neurocognitive consequences of hand augmentation
Authors: Kieliba Paulina , Clode Danielle , Maimon-Mor Roni O , Makin Tamar R.
Published: June 2020

From hand tools to cyborgs, humans have long been fascinated by the opportunities afforded by augmenting ourselves. Here, we studied how motor augmentation with an extra robotic thumb (the Third Thumb) impacts the biological hand representation in the brains of able-bodied people. Participants were tested on a variety of behavioural and neuroimaging tests designed to interrogate the augmented hand’s representation before and after 5-days of semi-intensive training. Training improved the Thumb’s motor control, dexterity and hand-robot coordination, even when cognitive load was increased or when vision was occluded, and resulted in increased sense of embodiment over the robotic Thumb. Thumb usage also weakened natural kinematic hand synergies. Importantly, brain decoding of the augmented hand’s motor representation demonstrated mild collapsing of the canonical hand structure following training, suggesting that motor augmentation may disrupt the biological hand representation. Together, our findings unveil critical neurocognitive considerations for designing human body augmentation.
The IMEx Coronavirus interactome: an evolving map of Coronaviridae-Host molecular interactions
Authors: Perfetto L , Pastrello C , Del-Toro N , Duesbury M , Iannuccelli M , Kotlyar M , Licata L , Meldal B , Panneerselvam K , Panni S , Rahimzadeh N , Ricard-Blum S , Salwinski L , Shrivastava A , Cesareni G , Pellegrini M , Orchard S , Jurisica I , Hermjakob HH , Porras P
Published: June 2020

The current Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has spurred a wave of research of nearly unprecedented scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions enables studying fine-grained resolution of the mechanisms behind the virus biology and the human organism response. Here we present a curated dataset of physical molecular interactions, manually extracted by IMEx Consortium curators focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of theCoronaviridaefamily. Currently, the dataset comprises over 2,200 binarized interactions extracted from 86 publications. The dataset can be accessed in the standard formats recommended by the Proteomics Standards Initiative (HUPO-PSI) at the IntAct database website (www.ebi.ac.uk/intact), and will be continuously updated as research on COVID-19 progresses.
PRER: A Patient Representation with Pairwise Relative Expression of Proteins on Biological Networks
Authors: İbrahim Kuru Halil , Buyukozkan Mustafa , Tastan Oznur
Published: June 2020

Changes in protein and gene expression levels are often used as features to predictive models such as survival prediction. A common strategy to aggregate information on individual proteins is to integrate the expression information with biological networks. We propose a novel patient representation in this work where we integrate proteins’ expression levels with the protein-protein interaction (PPI) networks. Patient representation with PRER (PairwiseRelativeExpressions withRandom walks) uses the neighborhood of a protein to capture the dysregulation patterns in protein abundance. Specifically, PRER computes a feature vector for a patient by comparing the source protein’s protein expression level with other proteins’ levels in its neighborhood. This neighborhood of the source protein is derived using a biased random-walk strategy on the network. We test PRER’s performance through a survival prediction task in 10 different cancers using random forest survival models. PRER representation yields a statistically significant predictive performance in 9 out of 10 cancer types when compared to a representation based on individual protein expression. We also identify important proteins that are not important in the models trained with the expression values but emerge as predictive in models trained with PRER features. The set of identified relations provides a valuable collection of biomarkers with high prognostic value. PRER representation can be used for other complex diseases and prediction tasks that use molecular expression profiles as input. PRER is freely available at:https://github.com/hikuru/PRER
Modulating Brain Rhythms of Pain using Transcranial Alternating Current Stimulation (tACS)? A Sham-controlled Study in Healthy Human Participants
Authors: May Elisabeth S. , Hohn Vanessa D. , Nickel Moritz M. , Tiemann Laura , Ávila Cristina Gil , Heitmann Henrik , Sauseng Paul , Ploner Markus
Published: June 2020

Pain protects the body. However, pain can also occur for longer periods without serving protective functions. Such chronic pain conditions are difficult to treat. Thus, a better understanding of the underlying neural mechanisms and new approaches for the treatment of pain are urgently needed. Here, we investigated a causal role of oscillatory brain activity for pain and explored the potential of transcranial alternating current stimulation (tACS) as a new treatment approach for pain. To this end, we investigated whether tACS can modulate pain and pain-related autonomic activity in 29 healthy human participants using a tonic heat pain paradigm as an experimental model of chronic pain. In 6 recording sessions, participants received tACS over prefrontal or somatosensory cortices at alpha or gamma frequencies or sham tACS. During tACS, pain ratings and autonomic responses were collected. TACS did not modulate pain intensity, the stability of pain ratings or the translation of the noxious stimulus into pain. Likewise, tACS did not change autonomic responses. Bayesian statistics further indicated a lack of tACS effects in most conditions. The only exception was alpha tACS over somatosensory cortex where evidence for tACS effects was inconclusive. Taken together, the present study did not find significant tACS effects on tonic experimental pain in healthy human participants. However, considering the conceptual plausibility of using tACS to modulate pain and the urgent need for novel pain treatments, further tACS studies are warranted. Based on the present findings, such studies might apply refined stimulation protocols targeting alpha oscillations in somatosensory cortices.
A yeast BiFC-seq method for genome-wide interactome mapping
Authors: Shang Limin , Zhang Yuehui , Liu Yuchen , Jin Chaozhi , Yuan Yanzhi , Tian Chunyan , Ni Ming , Bo Xiaochen , Zhang Li , Li Dong , He Fuchu , Wang Jian
Published: June 2020

Genome-wide physical protein-protein interaction (PPI) mapping remains a major challenge for current technologies. Here, we report a high-efficiency yeast bimolecular fluorescence complementation method coupled with next-generation DNA sequencing (BiFC-seq) for interactome mapping. We applied this technology to systematically investigate an intraviral network of Ebola virus (EBOV). Two-thirds (9/13) of known interactions of EBOV were recaptured and five novel interactions were discovered. Next, we used BiFC-seq method to map the interactome of the tumor protein p53. We identified 97 interactors of p53 with more than three quarters are novel. Furthermore, in more complex background, we screened potential interactors by pooling two BiFC-libraries together, and revealing a network of 229 interactions among 205 proteins. These results show that BiFC-seq is a highly sensitive, rapid and economical method in genome-wide interactome mapping.
The neurophysiological basis of short- and long-term ventriloquism aftereffects
Authors: Park Hame , Kayser Christoph
Published: June 2020

Our senses often receive conflicting multisensory information, which our brain reconciles by adaptive recalibration. A classic example is the ventriloquist aftereffect, which emerges following both long-term and trial-wise exposure to spatially discrepant multisensory stimuli. Still, it remains debated whether the behavioral biases observed following short- and long-term exposure arise from largely the same or rather distinct neural origins, and hence reflect the same or distinct mechanisms. We address this question by probing EEG recordings for physiological processes predictive of the single-trial ventriloquism biases following the exposure to spatially offset audio-visual stimuli. Our results support the hypothesis that both short- and long-term aftereffects are mediated by common neurophysiological correlates, which likely arise from sensory and parietal regions involved in multisensory inference and memory, while prolonged exposure to consistent discrepancies additionally recruits prefrontal regions. These results posit a central role of parietal regions in mediating multisensory spatial recalibration and suggest that frontal regions contribute to increasing the behavioral bias when the perceived sensory discrepancy is consistent and persistent over time.
CYCLODEXTRIN DERIVATIVE ENHANCES THE OPHTHALMIC DELIVERY OF POORLY SOLUBLE AZITHROMYCIN
Authors: Thakur Anil , Jain Sourabh , Pant Anjali , Sharma Akanksha , Kumar Rajiv , Sharma Gajanand , Singla Neha , Suttee Ashish , Kumar Santosh , Barnwal Ravi Pratap , Katare O.P. , Singh Gurpal
Published: June 2020

Azithromycin (AZM), a macrolide antibiotic used for the treatment of Chlamydial conjunctivitis, is less effective for the treatment of this disease due to its poor bioavailability (38%). Various alternatives have been developed for improving the physico-chemical properties (i.e., solubility) of the AZM without much success. To overcome the problems associated with AZM, an inclusion complex employing a modified cyclodextrin i.e., sulfobutylether-β-cyclodextrin (SBE-β-CD) was prepared and characterized by phase solubility studies, pXRD and FTIR techniques. The results portrayed the formation of the inclusion complex of AZM with sulfobutylether β-cyclodextrin (SBE-β-CD) in 1:2 molar stoichiometric ratios. This inclusion complex was later incorporated into a polymer matrix to prepare anin situgel. Various combinations of carbopol 934P and hydroxypropyl methylcellulose (HPMC K4M) polymers were used and evaluated by rheological andin vitrodrug release studies. The optimized formulation (F4), containing carbopol 934P 0.2% (w/v) and HPMC K4M 0.2% (w/v), was evaluated for clarity, pH, gelling capacity, drug content, rheological properties,in vitrodrug release pattern, ocular irritation test and antimicrobial efficacy. Finally, owing to the improved antimicrobial efficacy and increased residence time, AZM:SBE-β-CDin situgel was found to be a promising formulation for the efficient treatment of bacterial ocular disease.
Comparison of decidual vasculopathy in central and peripheral regions of placenta with implication of lateral growth and spiral artery remodeling
Authors: Zhang Peilin
Published: June 2020

Background

Decidual vasculopathy at late gestation was shown to be associated with spiral artery remodeling at implantation. How placental lateral growth is related to spiral artery remodeling in spatiotemporal fashion is to be investigated.

Design

The central and peripheral portions of 105 placentas with decidual vasculopathy at term were examined with or without preeclampsia to see if temporal vascular regeneration was present. Central and peripheral vasculopathy and central and peripheral regeneration were compared.

Result

Peripheral portion showed more decidual vasculopathy (88 of total 105, 83.8%) than central portion (72 of total 105, 68.6%, p=0.0018). However, central portion showed more vascular regeneration (51 of total 105, 48.6%) than peripheral portion (23 of total 105, 21.9%, p=0.0024). There is no difference in vasculopathy or regeneration with or without preeclampsia.

Conclusion

Spiral artery remodeling is non-synchronous during lateral growth and vascular regeneration. This spatiotemporal sequence may help interpretation of morphologic changes of decidual vasculopathy.