bluuebunny/crossref_metadata_2025 huggingface dataset:
Using next-generation sequencing of microRNAs to identify host and/or pathogen nucleic acid signatures in samples from children with biliary atresia – a pilot study
Authors: Smith Melvyn , Zuckerman Mark , Kandanearatchi Apsara , Thompson Richard , Davenport Mark
Published: June 2020

Biliary atresia (BA) is a progressive disease affecting infants resulting in inflammatory obliteration and fibrosis of the extra- and intra-hepatic biliary tree. BA may be grouped into type 1 isolated; type 2 syndromic, where other congenital malformations may be present; type 3 cystic BA, where there is cyst formation within an otherwise obliterated biliary tree; and cytomegalovirus-associated BA. The cause of BA is unclear, with immune dysregulation, inflammation and infection, particularly with cytomegalovirus (CMV), all implicated. In this study a total of 50/67 samples were tested for CMV DNA using quantitative real-time PCR. Ten liver tissue and 8 bile samples from 10 patients representing the range of BA types were also analysed by next-generation sequencing. CMV DNA was found in 8/50 (16 %) patients and a total of 265 differentially expressed microRNAs were identified. No statistically significant differences between the various types of BA were found. However, differences were identified in the expression patterns of 110 microRNAs in bile and liver tissue samples (P<0.05). A small number of bacterial and viral sequences were found, although their relevance to BA remains to be determined. No direct evidence of viral causes of BA were found, although clear evidence of microRNAs associated with hepatocyte and cholangiocyte differentiation together with fibrosis and inflammation were identified. These include miR-30 and the miR-23 cluster (liver and bile duct development) and miR-29, miR-483, miR-181, miR-199 and miR-200 (inflammation and fibrosis).
Arcobacter butzleri is an opportunistic pathogen: recurrent bacteraemia in an immunocompromised patient without diarrhoea
Authors: Soelberg Kerstin K. , Danielsen Trille K. L. , Martin-Iguacel Raquel , Justesen Ulrik S.
Published: June 2020

Introduction.

Arcobacter butzleri

is attracting increasing interest due to its possible pathogenic properties. Researchers have described cases in which

A. butzleri

is isolated in stool samples from patients with gastrointestinal symptoms, mostly diarrhoea. The relevance of adding our case to the literature lies in its description of recurrent

A. butzleri

bacteraemia in a patient without diarrhoea.

Case presentation. An immunocompromised patient was hospitalized three times within 12 months due to A. butzleri-induced bacteraemia. At no time did the patient experience diarrhoea even though examination of stool samples showed growth of

A. butzleri

. The isolate was susceptible to gentamicin, colistin and tetracyclines. The patient was successfully treated with doxycycline.

Conclusion. For the first time in the literature we describe recurrent

A. butzleri

bacteraemia in a patient without diarrhoea. This case supports the classification of

A. butzleri

as an opportunistic pathogenic species, which clinical microbiology laboratories should be able to identify.
Characterization of Ba813 harbouring Bacillus cereus in patients with haematological malignancy and hospital environments at a medical centre in Japan
Authors: Aoyagi Tetsuji , Kishihara Yasuhiro , Ogawa Miho , Ito Yuki , Tanaka Sakie , Kobayashi Ryozo , Tokuda Koichi , Kaku Mistuo
Published: June 2020

Introduction.
Bacillus cereus harbouring Ba813, a specific chromosomal marker of Bacillus anthtacis, is found in patients with severe manifestations and causes nosocomial outbreaks.

Aim. We assessed the genetic characteristics and virulence of Ba813(+)

B. cereus

in a hospital setting.

Methodology. Three neutropenic patients with haematological malignancy developed

B. cereus

bacteraemia within a short period. Fifteen

B. cereus

were isolated from different sites in a haematology ward. A total of 18 isolates were evaluated for Ba813- and

B. anthracis

-related virulence, food poisoning-related virulence, genetic diversity, bacteria motility and biofilm formation.

Results.
Ba813(+)

B. cereus

was detected in 33 % (1/3) of patients and 66 % (9/15) of the hospital environment. The 18 strains were divided into 2 major clusters (clade 1 and clade 2), and 14 strains were classified into clade 1. All Ba813(+) strains, including four sequence types, were classified into clade 1/the cereus III lineage, which is most closely related to the anthracis lineage. Two strains belonging to clade 1/non-cereus III carried the

B. anthracis

-associated cap gene, but not Ba813. B. cereus, including Ba813(+) strains, had significantly lower prevalence of enterotoxin genes than clade 2 strains. In clade 1,

B. cereus

, Ba813(+) strains showed significantly higher swimming motility and biofilm formation ability than Ba813(−) strains.

Conclusion.
Ba813(+)

B. cereus

, which are genetically closely related to

B. anthracis

, were abundant in a haematological ward. Ba813(+)

B. cereus

with high motility and biofilm formation abilities may spread easily in hospital environments, and could become a hospital-acquired infection.
Antimicrobial resistance profiles of diarrhoeagenic Escherichia coli isolated from travellers returning to the UK, 2015–2017
Authors: Boxall Megan D. , Day Martin R. , Greig David R. , Jenkins Claire
Published: June 2020

Introduction. Diarrhoeagenic

Escherichia coli

(DEC) are difficult to distinguish from non-pathogenic commensal

E. coli

using traditional culture methods. The implementation of PCR targeting specific virulence genes characteristic of the five DEC pathotypes, has improved the detection of DEC in faecal specimens from patients with symptoms of gastrointestinal disease.

Aim. Antimicrobial resistance (AMR) profiles of 660 strains of DEC isolated between 2015 and 2017 from UK travellers reporting symptoms of gastrointestinal disease were reviewed to look for evidence of emerging AMR associated with travellers’ diarrhoea.

Methodology. All isolates of DEC were sequenced, and sequence type, serotype, pathotype markers and AMR profiles were derived from the genome data.

Results. A travel history was provided for 54.1 % (357/660) of cases, of which 77.0 % (275/357) reported travel outside the UK within 7 days of onset of symptoms, and 23.0 % (82/357) reported no travel in that time frame. Of the 660 strains of DEC in this study, 265 (40.2 %) samples were identified as EAEC, 48 (7.3 %) as EIEC, 61 (9.2 %) were ETEC and 286 (43.3 %) were EPEC. EPEC caused the highest percentage of infections in children (40.6 %) whilst the highest proportion of cases reporting recent travel were infected with ETEC (86.1 %). There were 390/660 (59.0 %) isolates resistant to at least one antimicrobial on the panel tested (EIEC, 81.3 %; ETEC, n=65.6 %; EAEC, n=73.2 %; EPEC, 40.9 %) and 265/660 (40.2 %) were multidrug-resistant (EIEC, 33.3 %; ETEC, 32.8 %; EAEC, 56.2 %; EPEC, 28.0 %). Genes conferring resistance to the beta-lactams and fluroquinolones were highest in the EAEC pathotype, 56.6 and 60.7%, respectively.

Conclusions. Increasing MDR, along with resistance to the fluroquinolones and the third-generation cephalosporins, in DEC causing travellers’ diarrhoea provides further evidence for the need to restrict the use of antimicrobial agents and continuous monitoring.
Hyaluronic acid for tissue and bone regeneration after tooth extraction. Systematic review and meta-analysis
Authors: Lai Shuheng , Novillo Francisco , Cárdenas Geovanna , Verdugo Francisca , Rada Gabriel
Published: June 2020

Objective

The objective of this systematic review is to assess the effectiveness and safety of Hyaluronic Acid (HA) on tissue and bone regeneration after tooth extraction.

Data Sources

We will conduct a comprehensive search in Epistemonikos, PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, the International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, US National Institutes of Health (NIH) and grey literature, to identify all relevant randomized controlled trials regardless of language or publication status (published, unpublished, in press and in progress).

Eligibility Criteria for Selecting Studies and Methods

We will include randomized trials evaluating the effect of HA on tissue and bone regeneration after tooth extraction. Two reviewers will independently screen each study for eligibility, data extraction, and assess the risk of bias. We will pool the results using meta-analysis and will apply the GRADE system to assess the certainty of the evidence for each outcome.

Ethics and Dissemination

No ethics approval is considered necessary. The results of this review will be disseminated via peer-reviewed publications, social networks, and traditional media.

PROSPERO Registration ID

CRD42020150285
High-Throughput Digitization of Analog Human Echocardiography Data
Authors: Kwan Alan C. , Salto Gerran , Demosthenes Emmanuella , Lehman Birgitta T. , Osypiuk Ewa , Stantchev Plamen , Vasan Ramachandran S. , Cheng Susan
Published: June 2020

Echocardiographic imaging data has been acquired for adult participants of a longitudinal community-based epidemiological cohort study at serial examinations between 1987 and 1998. The original image acquisition approach was analog with storage of moving images on Video Home System (VHS) tapes. Accordingly, we designed and implemented a standardized methodology for digitizing, anonymizing, and organizing these analog data to enable contemporary image-based analyses. Herein, we describe the overall methodology and the operational workflow, quality control, Health Insurance Portability and Accountability Act compliance, and data formatting issues that we addressed. We present this method as an accessible pipeline for enabling digitization of historical imaging data, originally acquired from large cohort studies, in order to preserve and repurpose them for application of advanced and continually evolving image analytical techniques. Such pipelines are critical not only for data conservation but are also invaluable for prospective analyses of imaging phenotypes in relation to already-accrued longitudinal outcomes in community-based cohorts that have been under careful surveillance over up to several decades of follow up.
A Fully Automated Deep Learning-based Network For Detecting COVID-19 from a New And Large Lung CT Scan Dataset
Authors: Rahimzadeh Mohammad , Attar Abolfazl , Sakhaei Seyed Mohammad
Published: June 2020

Abstract

COVID-19 is a severe global problem, and AI can play a significant role in preventing losses by monitoring and detecting infected persons in early-stage. This paper aims to propose a high-speed and accurate fully-automated method to detect COVID-19 from the patient’s CT scan images. We introduce a new dataset that contains 48260 CT scan images from 282 normal persons and 15589 images from 95 patients with COVID-19 infections. At the first stage, this system runs our proposed image processing algorithm to discard those CT images that inside the lung is not properly visible in them. This action helps to reduce the processing time and false detections. At the next stage, we introduce a novel method for increasing the classification accuracy of convolutional networks. We implemented our method using the ResNet50V2 network and a modified feature pyramid network alongside our designed architecture for classifying the selected CT images into COVlD-19 or normal with higher accuracy than other models. After running these two phases, the system determines the condition of the patient using a selected threshold. We are the first to evaluate our system in two different ways. In the single image classification stage, our model achieved 98.49% accuracy on more than 7996 test images. At the patient identification phase, the system correctly identified almost 234 of 245 patients with high speed. We also investigate the classified images with the Grad-CAM algorithm to indicate the area of infections in images and evaluate our model classification correctness.
Oscillations in USA COVID-19 Incidence and Mortality Data reflect societal factors
Authors: Bergman Aviv , Sella Yehonatan , Agre Peter , Casadevall Arturo
Published: June 2020

The COVID-19 pandemic currently in process differs from other infectious disease calamities that have previously plagued humanity in the vast amount of information that is produces each day, which includes daily estimates of the disease incidence and mortality data. Apart from providing actionable information to public health authorities on the trend of the pandemic, the daily incidence reflects the process of disease in a susceptible population and thus reflects the pathogenesis of COVID-19, the public health response and diagnosis and reporting. Both daily new cases and daily mortality data in the US exhibit periodic oscillatory patterns. By analyzing NYC and LA testing data, we demonstrate that this oscillation in the number of cases can be strongly explained by the daily variation in testing. This seems to rule out alternative hypotheses such as increased infections on certain days of the week as driving this oscillation. Similarly, we show that the apparent oscillation in mortality in the US data is mostly an artifact of reporting, which disappears in datasets that record death by episode date, such as the NYC and LA datasets. Periodic oscillations in COVID-19 incidence and mortality data reflect testing and reporting practices and contingencies. Thus, these contingencies should be considered first prior to suggesting social or biological mechanisms.
Jinhua Qinggan granule, a Chinese herbal medicine against COVID-19, induces rapid changes in the plasma levels of IL-6 and IFN-γ
Authors: Kageyama Yasunari , Aida Koichi , Kawauchi Kimihiko , Morimoto Masafumi , Ebisui Tomoka , Akiyama Tetsu , Nakamura Tsutomu
Published: June 2020

Background

Currently, effective vaccines or specific therapeutic agents against COVID-19 are not available. However, in China, traditional Chinese herbal medicines have provided therapeutic benefit to patients with COVID-19. Jinhua Qinggan granule (JHQGG) is a Chinese multi-herbal formula previously developed for the treatment of H1N1 influenza and has been encouraged for patients clinically suspected of COVID-19 during medical observation. However, the immunological mechanism for the efficacy of JHQGG has not been confirmed.

Objectives

We thus examined whether the administration of JHQGG affects hematological and immunological measures in healthy individuals.

Method

We enrolled 18 healthy volunteers, all of whom tested negative for antibodies to SARS-CoV-2. Peripheral blood samples were collected 1 h after oral administration of JHQGG and subjected to hematological, biochemical, and cytokine tests.

Results

JHQGG rapidly induced a significant decrease in the plasma level of IL-6 and an increase in the plasma level of IFN-γ.

Conclusions

Our finding suggests that the therapeutic efficacy of JHQGG against COVID-19 is, in part, associated with its rapid immunomodulatory activity.
Cytolethal Distending Toxin: from mitotic DNA damage to cGAS-dependent pro-inflammatory response
Authors: Pons Benoît J. , Pettes-Duler Aurélie , Naylies Claire , Taieb Frédéric , Hashim Saleha , Tadrist Soraya , Lippi Yannick , Mirey Gladys , Vignard Julien
Published: June 2020

The Cytolethal Distending Toxin (CDT) is a bacterial genotoxin that activates the DNA damage response and induces inflammatory signatures in host cells, but the precise relationship between these outcomes has not been addressed so far. CDT induces a singular time-dependent increase of DNA damage and cell cycle defects, questioning on possible impaired response to this toxin over the cell cycle. Here, we identify mitosis as a crucial phase during CDT intoxination. Despite active cell cycle checkpoints and in contrast to other DNA damaging agents, CDT-exposed cells reach mitosis where they accumulate massive DNA damage, resulting in chromosome fragmentation and micronucleus formation. These micronuclei are recognized by cGAS that elicits an inflammatory signature resulting in cell distention and senescence. Our results unravel for the first time the mitotic consequences of CDT genotoxic activity and relate them to pro-inflammatory cellular response. These findings may have important implications during bacterial infection regarding CDT-mediated immunomodulatory and tumorigenic processes.
Pregnancy associated plasma protein-aa regulates endoplasmic reticulum-mitochondria associations
Authors: Alassaf Mroj , Halloran Mary
Published: June 2020

The endoplasmic reticulum (ER) and mitochondria form close physical associations to facilitate calcium transfer, thereby regulating mitochondrial function and dynamics. For neurons with high metabolic demands, such as sensory hair cells, precise regulation of ER-mitochondria associations is especially critical for cell survival. We previously identified the secreted metalloprotease Pregnancy associated plasma protein-aa (Pappaa) as a novel regulator of mitochondrial function in zebrafish lateral line hair cells (Alassaf et al., 2019). Here, we show thatpappaamutant hair cells exhibit excessive and abnormally close ER-mitochondria associations, suggesting increased ER-mitochondria calcium transfer. Indeed, we find thatpappaamutant hair cells are more vulnerable to pharmacological induction of ER-calcium release. Additionally,pappaamutant hair cells display ER stress and dysfunctional downstream processes of the ER-mitochondria axis including mitochondrial fragmentation and autophagy. Together our results support a model in which Pappaa regulates mitochondrial function, at least in part, by regulating ER-mitochondria associations.
Vigilance response of a key prey species to anthropogenic and natural threats in Detroit
Authors: Lima Samantha , Gámez Siria , Arringdale Nathaniel , Harris Nyeema C.
Published: June 2020

Rapid urbanization coupled with increased human activity induces pressures that affect predator-prey relations through a suite of behavioral mechanisms, including alteration of avoidance and coexistence dynamics. Synergisms of natural and anthropogenic threats existing within urban environments exacerbate the necessity for species to differentially modify behavior to each risk. Here, we explore the behavioral response of a key prey species, cottontail rabbits (Sylvilagus floridanus), to pressures from humans, domestic dogs, and a natural predator, coyotes (Canis latrans) in a human-dominated landscape. We conducted the first camera survey in urban parks throughout Detroit, Michigan in 2017-2020 to assess vigilance response corresponding to a heterogeneous landscape created from variation in the occupancy of threats. We predicted a scaled response where cottontail rabbits would be most vigilant in areas with high coyote activity, moderately vigilant in areas with high domestic dog activity, and the least vigilant in areas of high human activity. From 8,165 independent cottontail rabbit detections in Detroit across 11,616 trap nights, one-third were classified as vigilant. We found vigilance behavior increased with coyote occupancy and in locations with significantly high domestic dog activity, but found no significant impact of human occupancy or their spatial hotspots. We also found little spatial overlap between rabbits and threats, suggesting rabbits invest more in spatial avoidance; thus, less effort is required for vigilance. Our results elucidate strategies of a prey species coping with various risks to advance our understanding of the adaptability of wildlife in urban environments. In order to promote coexistence between people and wildlife in urban greenspaces, we must understand and anticipate the ecological implications of human-induced behavioral modifications.
Transcriptional profiling reveals T cells cluster around neurons injected withToxoplasma gondiiproteins
Authors: Merritt Emily F. , Johnson Hannah J. , Wong Z. Sheen , Buntzman Adam S. , Conklin Austin C. , Cabral Carla M. , Romanoski Casey E. , Boyle Jon P. , Koshy Anita A.
Published: June 2020

Toxoplasma gondii’s tropism for and persistence in the CNS underlies the symptomatic diseaseToxoplasmacauses in humans. Our recent work has shown that neurons are the primary CNS cell with whichToxoplasmainteracts and infectsin vivo. This predilection for neurons suggests thatToxoplasma’s persistence in the CNS depends specifically upon parasite manipulation of the host neurons. Yet, most work onToxoplasma-host cell interactions has been donein vitroand in non-neuronal cells. We address this gap by utilizing ourToxoplasma-Cre system that allows permanent marking and tracking of neurons injected with parasite effector proteinsin vivo. Using laser capture microdissection (LCM) and RNA-seq, we isolated and transcriptionally profiledToxoplasma-injected neurons (TINs), Bystander neurons (nearby non-Toxoplasmainjected neurons), and neurons from uninfected mice (controls). These profiles show that TINs transcriptomes significantly differ from the transcriptomes of Bystander and control neurons and that much of this difference is driven by increased levels of transcripts from immune cells, especially CD8+T cells and monocytes. These data suggest that when we used LCM to isolate neurons from infected mice, we also picked up fragments of CD8+T cells and monocytes clustering in extreme proximity around TINs and, to a lesser extent, Bystander neurons. In addition, we found thatToxoplasmatranscripts were primarily found in the TINs transcriptome, not in the Bystander transcriptome. Collectively, these data suggest that, contrary to common perception, neurons that directly interact with or harbor parasites can be recognized by CD8+T cells.
Chimeric synthetic reference standards enable cross-validation of positive and negative controls in SARS-CoV-2 molecular tests
Authors: Madala Bindu Swapna , Reis Andre L. M. , Deveson Ira W. , Rawlinson William , Mercer Tim R.
Published: June 2020

DNA synthesisin vitrohas enabled the rapid production of reference standards. These are used as controls, and allow measurement and improvement of the accuracy and quality of diagnostic tests. Current reference standards typically represent target genetic material, and act only as positive controls to assess test sensitivity. However, negative controls are also required to evaluate test specificity. Using a pair of chimeric A/B RNA standards, this allowed incorporation of positive and negative controls into diagnostic testing for the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The chimeric standards constituted target regions for RT-PCR primer/probe sets that are joined in tandem across two separate synthetic molecules. Accordingly, a target region that is present in standard A provides a positive control, whilst being absent in standard B, thereby providing a negative control. This design enables cross-validation of positive and negative controls between the paired standards in the same reaction, with identical conditions. This enables control and test failures to be distinguished, increasing confidence in the accuracy of results. The chimeric A/B standards were assessed using the US Centers for Disease Control real-time RT-PCR protocol, and showed results congruent with other commercial controls in detecting SARS CoV-2 in patient samples. This chimeric reference standard design approach offers extensive flexibility, allowing representation of diverse genetic features and distantly related sequences, even from different organisms.
An imperfect tool: contact tracing could provide valuable reductions in COVID-19 transmission if good adherence can be achieved and maintained
Authors: Davis Emma L. , Lucas Tim C. D. , Borlase Anna , Pollington Timothy M. , Abbott Sam , Ayabina Diepreye , Crellen Thomas , Hellewell Joel , Pi Li ,   CMMID COVID-19 working group, Medley Graham F. , Hollingsworth T. Déirdre , Klepac Petra
Published: June 2020

Emerging evidence suggests that contact tracing has had limited success in the UK in reducing the R number across the COVID-19 pandemic. We investigate potential pitfalls and areas for improvement by extending an existing branching process contact tracing model, adding diagnostic testing and refining parameter estimates. Our results demonstrate that reporting and adherence are the most important predictors of programme impact but tracing coverage and speed plus diagnostic sensitivity also play an important role. We conclude that well-implemented contact tracing could bring small but potentially important benefits to controlling and preventing outbreaks, providing up to a 15% reduction in R, and reaffirm that contact tracing is not currently appropriate as the sole control measure.
Longitudinal effect of gestational age on the developmental trajectory of social competence difficulties from early childhood to mid-adolescence: Evidence from the UK Millennium Cohort
Authors: Hosozawa Mariko , Cable Noriko , Kelly Yvonne , Sacker Amanda
Published: June 2020

Background

Preterm birth and maternal psychological distress are associated with an increased risk for social competence difficulties; however, little is known about how this risk changes over time and across gestational age. This study aimed to examine mean developmental trajectories of social competence difficulties from early childhood to mid- adolescence by gestational age groups: very preterm (VP, <32 weeks), moderate-to-late preterm (MLP, 32-36 weeks), early-term (37-38 weeks) and full-term (39-41 weeks) and to assess the mediating effect of maternal psychological distress during infancy on the social competence difficulties trajectories.

Methods

Data were analysed on 15,821 participants from the UK Millennium Cohort Study participants, a nationally-representative birth cohort. Social competence difficulties were assessed by parent report when the participants were aged 3, 5, 7, 11 and 14 years. Maternal psychological distress was self-rated when the children were 9 months of age. Data were modelled using latent growth curve analysis.

Results

The developmental trajectories of social competence difficulties were u-shaped in all groups showing a decline from age 3 to 7, followed by a stable low period and then an increase during adolescence. VP children (n=173) showed pronounced difficulties throughout (b=0.94, SE=0.36 at age 14). MLP children (n=1,130) and early-term children (n=3,232) showed greater difficulties compared with their full-term peers around age 7, which resolved by age 14 (b=0.20, SE=0.13; 0.03, 0.07, respectively). Maternal psychological distress during infancy mediated 20% of the above association for VP.

Conclusions

The effect of gestational age on developmental trajectories of social competence difficulties can be dose-response. Monitoring and providing support on social development throughout childhood and into their adolescence and treating early maternal psychological distress may benefit preterm children, particularly those born VP.
Kinetics of the humoral immune response to SARS-CoV-2: comparative analytical performance of seven commercial serology tests
Authors: Herroelen Pauline H. , Martens Geert A. , De Smet Dieter , Swaerts Koen , Decavele An-Sofie
Published: June 2020

Background

SARS-CoV-2 serology tests are clinically useful to document a prior SARS-CoV-2 infection in patients with no or inconclusive PCR results and suspected COVID-19 disease or sequelae. Data are urgently needed to select the assays with optimal sensitivity at acceptable specificity.

Methods

A comparative analysis of analytical sensitivity was performed of seven commercial SARS-CoV-2 serology assays on 171 sera from 135 subjects with PCR-confirmed SARS-CoV-2 infection, composed of 71 patients hospitalized for COVID-19 pneumonia and 64 healthcare workers with paucisymptomatic infections. The kinetics of IgA/IgM/IgG seroconversion to viral N-and S-protein epitopes were studied from 0 to 54 days after symptom onset. Specificity was verified on 57 pre-pandemic samples.

Results

Wantai SARS-COV-2 Ab ELISA and Orient Gene COVID-19 IgG/IgM Rapid Test achieved a superior overall sensitivity. Elecsys Anti-SARS-CoV-2 assay and EUROIMMUN Anti-SARS-CoV-2 combined IgG/IgA also showed acceptable sensitivity (>95%) versus the consensus result of all assays from 10 days post symptom onset. Optimal specificity (>98%) was achieved only by Wantai SARS-COV-2 Ab ELISA, Elecsys Anti-SARS-CoV-2 assay and Innovita 2019-nCoV Ab rapid test. LIAISON SARS-CoV-2 S1/S2 IgG showed a significantly lower sensitivity as compared to all other assays. Lack of seroconversion by any test was seen in 1.4% of hospitalized and 4.7% of paucisymptomatic infections. Within 10 days from symptom onset, only the Wantai SARS-COV-2 Ab ELISA has acceptable sensitivity.

Conclusions

Wantai SARS-COV-2 Ab ELISA and Elecsys Anti-SARS-CoV-2 assays are suitable for sensitive and specific screening of a SARS-CoV-2 infection from 10 days after symptom onset.

Brief summary

There is an urgent need for SARS-CoV-2 serology tests for the sensitive and specific detection of prior SARS-CoV-2 infection as a complementary diagnostic tool to molecular testing. Various commercial assays are becoming available but comparison of their relative performance is difficult unless they are head-to-head evaluated. Here we compared seven commercial assays on sera equally composed of mild and severe PCR-confirmed SARS-CoV-2 infections. Our analysis indicates a superior performance of the Wantai SARS-COV-2 ELISA for total antibodies to the S-RBD domain. Also, the Elecsys Anti-SARS-CoV-2 assay for total antibodies to the N-protein shows good performance for high-throughput screening.
ANGPTL8 protein-truncating variant and the risk of coronary disease, type 2 diabetes and adverse effects
Authors: Helkkula Pyry , Kiiskinen Tuomo , Havulinna Aki S. , Karjalainen Juha , Koskinen Seppo , Salomaa Veikko , FinnGen  , Daly Mark J. , Palotie Aarno , Surakka Ida , Ripatti Samuli
Published: June 2020

Protein-truncating variants (PTVs) affecting dyslipidemia risk may point to therapeutic targets for cardiometabolic disease. Our objective was to identify PTVs that associated with both lipid levels and cardiometabolic disease risk and assess their possible associations with risks of other diseases. To achieve this aim, we leveraged the enrichment of PTVs in the Finnish population and tested the association of low-frequency PTVs in 1,209 genes with serum lipid levels in the Finrisk Study (n = 23,435). We then tested which of the lipid-associated PTVs also associated with risks of cardiometabolic diseases or 2,264 disease endpoints curated in the FinnGen Study (n = 176,899). Three PTVs were associated with both lipid levels and the risk of cardiometabolic disease: triglyceride-lowering variants in ANGPTL8 (−24.0[-30.4 to −16.9] mg/dL per rs760351239-T allele, P = 3.4× 10−9) and ANGPTL4 (−14.4[-18.6 to −9.8] mg/dL per rs746226153-G allele, P = 4.3 × 10−9) and the HDL cholesterol-elevating variant in LIPG (10.2[7.5 to 13.0] mg/dL per rs200435657-A allele, P = 5.0 × 10−13). The risk of type 2 diabetes was lower in carriers of ANGPTL8 (odds ratio [OR] = 0.67[0.47-0.92], P = 0.01), ANGPTL4 (OR = 0.70[0.60-0.82], P = 1.4× 10−5) and LIPG (OR = 0.67[0.48-0.91], P = 0.01) PTVs than in noncarriers. Moreover, the odds of coronary artery disease were 44% lower in carriers of a PTV in ANGPTL8 (OR = 0.56[0.38-0.83], P = 0.004). Finally, the phenome-wide scan of the ANGPTL8 PTV showed a markedly higher associated risk of esophagitis (585 cases, OR = 174.3[17.7-1715.1], P = 9.7 × 10−6) and sensorineural hearing loss (12,250 cases, OR = 2.45[1.63-3.68], P = 1.8 × 10−5). The ANGPTL8 PTV carriers were less likely to use statin therapy (53,518 cases, OR = 0.53[0.41-0.71], P = 1.2 × 10−5). Our findings provide genetic evidence of potential long-term efficacy and safety of therapeutic targeting of dyslipidemias.
Private Health Sector in India: Ready and willing, yet underutilized in the Covid-19 pandemic
Authors: Davalbhakta Samira , Sharma Supriya , Gupta Shefali , Agarwal Vishwesh , Pandey Gaurav , Misra Durga Prasanna , Naik Bijaya Nanda , Goel Ashish , Gupta Latika , Agarwal Vikas
Published: June 2020

Background

The private medical sector is a resource that must be estimated for efficient inclusion into public healthcare during pandemics.

Methods

A survey was conducted among private healthcare workers to ascertain their views on the potential resources that can be accessed from the private sector and methods to do the same.

Results

There were 213 respondents, 80% of them being doctors. Nearly half (47.4%) felt that the contribution from the private medical sector has been suboptimal. Areas suggested for improved contributions by the private sector related to patient care (71.8%) and provision of equipment (62.4%), with fewer expectations (39.9%) on the research front. Another area of deemed support was maintaining continuity of care for non-COVID patients using virtual consultation services (77.4%), tele-consultation being the preferred option (60%). 58.2% felt that the Government had not involved the private sector adequately; and 45.1% felt they should be part of policy-making.

Conclusion

A streamlined pathway to facilitate the private sector to join hands with the public sector for a national cause is the need of the hour. Through our study, we have identified gaps in the current contribution by the private sector and identified areas in which they could contribute, by their own admission.
Construction of High Content Nanobody Library in Mammalian Cells by Linear-double-stranded DNA Based Strategies
Authors: Zhao Yanjie , Su Weijun , Li Shuai
Published: June 2020

Here, we developed two novel methods to construct high content nanobody library in mammalian cells. For the first method, we employed alinear-double-stranded DNAbasedAND-gate (LBAG) strategy. Upstream- and downstream-linear-double-stranded DNAs (ldsDNAs), containing identical overlapping sequences, were co-transfected into cultured cell lines to conduct AND-gate calculation to form intact nanobody expression cassette. For the second method, we generated full-length nanobody expression ldsDNA byin vitroligation of restrict cut up- and down-stream ldsDNAs. Then the ldsDNAs were directly transfected into mammalian cells to express nanobody library. Both methods generated over a million different nanobody sequences as revealed by high-throughput sequencing (HTS).
Speech intelligibility with various head-related transfer functions: A computational modeling approach
Authors: Ahrens Axel , Cuevas-Rodriguez Maria , Brimijoin W. Owen
Published: June 2020

Speech intelligibility is known to be affected by the relative spatial position between target and interferers. The benefit of a spatial separation is, along with other factors, related to the head-related transfer function (HRTF). The HRTF is individually different and thus, the cues that improve speech intelligibility might also be different. In the current study an auditory model was employed to predict speech intelligibility with a variety of HRTFs. The predicted speech intelligibility was found to vary across HRTFs. Thus, individual listeners might have different access to cues that are important for speech intelligibility.
Active foot placement control ensures stable gait: Effect of constraints on foot placement and ankle moments
Authors: van Leeuwen A.M. , van Dieën J.H. , Daffertshofer A. , Bruijn S.M.
Published: June 2020

Step-by-step foot placement control, relative to the center of mass (CoM) kinematic state, is generally considered a dominant mechanism for maintenance of gait stability. By adequate (mediolateral) positioning of the center of pressure with respect to the CoM, the ground reaction force generates a moment that prevents falling. In healthy individuals, foot placement is complemented mainly by ankle moment control ensuring stability. To evaluate possible compensatory relationships between step-by-step foot placement and complementary ankle moments, we investigated the degree of (active) foot placement control during steady-state walking, and under either foot placement-, or ankle moment constraints. Thirty healthy participants walked on a treadmill, while full-body kinematics, ground reaction forces and EMG activities were recorded. As a replication of earlier findings, we first showed step-by-step foot placement is associated with preceding CoM state and hip ab-/adductor activity during steady-state walking. Tight control of foot placement appears to be important at normal walking speed because there was a limited change in the degree of foot placement control despite the presence of a foot placement constraint. At slow speed, the degree of foot placement control decreased substantially, suggesting that tight control of foot placement is less essential when walking slowly. Step-by-step foot placement control was not tightened to compensate for constrained ankle moments. Instead compensation was achieved through increases in step width and stride frequency.
Neuro-computational mechanisms of action-outcome learning under moral conflict
Authors: Fornari L. , Ioumpa K. , Nostro A. D. , Evans N. J. , De Angelis L. , Paracampo R. , Gallo S. , Spezio M. , Keysers C. , Gazzola V.
Published: June 2020

Predicting how actions result in conflicting outcomes for self and others is essential for social functioning. We tested whether Reinforcement Learning Theory captures how participants learn to choose between symbols that define a moral conflict between financial self-gain and other-pain. We tested whether choices are better explained by model-free learning (decisions based on combined historical values of past outcomes), or model-based learning (decisions based on the current value of separately expected outcomes) by including trials in which participants know that either self-gain or other-pain will not be delivered. Some participants favored options benefiting themselves, others, preventing other-pain. When removing the favored outcome, participants instantly altered their choices, suggesting model-based learning. Computational modelling confirmed choices were best described by model-based learning in which participants track expected values of self-gain and other-pain separately, with an individual valuation parameter capturing their relative weight. This valuation parameter predicted costly helping in an independent task. The expectations of self-gain and other-pain were also biased: the favoured outcome was associated with more differentiated symbol-outcome probability reports than the less favoured outcome. FMRI helped localize this bias: signals in the pain-observation network covaried with pain prediction errors without linear dependency on individual preferences, while the ventromedial prefrontal cortex contained separable signals covarying with pain prediction errors in ways that did and did not reflected individual preferences.
Nectar larceny in the trainbearers (Lesbia, Trochilidae)
Authors: Igić Boris , Nguyen Ivory , Fenberg Phillip B.
Published: June 2020

Many flower visitors engage in floral larceny, a suite of so-called ‘illegitimate’ visits in which foragers take nectar without providing pollination services. The data on prevalence of illegitimate visits among hummingbirds, as well as the total proportion of foraging and diet that such visits comprise is broadly lacking. Here, we report the occurrence of nectar larceny in both currently recognized species of trainbearers and analyze the proportion of plant visits categorized by mode of interaction as: primary robbing, secondary robbing, theft, and/or pollination. To the best of our knowledge, we provide the first published report identifying robbing in these species. We augment our original field observations using a trove of data from citizen science databases and literature. Although it is difficult to distinguish primary vs. secondary robbing and theft vs. pollination, we conservatively estimate that ca. 40% of the recorded nectar foraging visits involve nectar robbing. Males appear to engage in robbing marginally more than females, but further studies are necessary to confidently examine the multi-way interactions among sex, species, mode of visitation, and other factors. We discuss the significance of these findings in the context of recent developments in study of nectar foraging, larceny, and pollination from both avian and plant perspectives.
NMDAR-mediated transcriptional control of gene expression during the development of medial ganglionic eminence-derived interneurons
Authors: Mahadevan Vivek , Mitra Apratim , Zhang Yajun , Yuan Xiaoqing , Peltekian Areg , Chittajallu Ramesh , Esnault Caroline , Maric Dragan , Rhodes Christopher , Pelkey Kenneth A. , Dale Ryan , Petros Timothy J. , McBain Chris J.
Published: June 2020

Medial ganglionic eminence (MGE)-derived parvalbumin (PV)+, somatostatin (SST)+ and Neurogliaform (NGFC)-type cortical and hippocampal interneurons, have distinct molecular, anatomical and physiological properties. However, the molecular mechanisms regulating their diversity remain poorly understood. Here, via single-cell transcriptomics, we show that the obligate NMDA-type glutamate receptor (NMDAR) subunit geneGrin1mediates subtype-specific transcriptional regulation of gene expression in MGE-derived interneurons, leading to altered subtype abundances. Notably, MGE-specific conditionalGrin1loss results in a systemic downregulation of diverse transcriptional, synaptogenic and membrane excitability regulatory programs. These widespread gene expression abnormalities mirror aberrations that are typically associated with neurodevelopmental disorders, particularly schizophrenia. Our study hence provides a road map for the systematic examination of NMDAR signaling in interneuron subtypes, revealing potential MGE-specific genetic targets that could instruct future therapies of psychiatric disorders.
Nonlinearities in retinal bipolar cells shape the encoding of artificial and natural stimuli
Authors: Schreyer Helene Marianne , Gollisch Tim
Published: June 2020

The retina dissects the visual scene into parallel feature channels, and bipolar cells are speculated to play a key role in this signal separation. Yet, bipolar cells are traditionally viewed as simple, linear neurons. Here, using the salamander retina, we investigated the hypothesis of linear signal processing in bipolar cells by intracellularly recording their voltage signals under artificial and natural visual stimuli. We observed nonlinear representation of contrast and, unexpectedly, also nonlinear spatial integration in a sizable fraction of bipolar cells. Furthermore, linear receptive field models fail to describe responses of nonlinear bipolar cells to spatially structured artificial and natural stimuli. The nonlinear properties occur in the receptive field center and may be cell-type specific, with stronger effects in transient than sustained bipolar cells. Thus, our data suggest that nonlinear signal pooling starts earlier than previously thought, that is, before signal integration in bipolar cells.
Remdesivir but not famotidine inhibits SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids
Authors: Krüger Jana , Groß Rüdiger , Conzelmann Carina , Müller Janis A. , Koepke Lennart , Sparrer Konstantin M. J. , Schütz Desiree , Seufferlein Thomas , Barth Thomas F.E. , Stenger Steffen , Heller Sandra , Kleger Alexander , Münch Jan
Published: June 2020

Gastrointestinal symptoms in COVID-19 are associated with prolonged symptoms and increased severity. We employed human intestinal organoids derived from pluripotent stem cells (PSC-HIOs) to analyze SARS-CoV-2 pathogenesis and to validate efficacy of specific drugs in the gut. Certain, but not all cell types in PSC-HIOs express SARS-CoV-2 entry factors ACE2 and TMPRSS2, rendering them susceptible to SARS-CoV-2 infection. Remdesivir, a promising drug to treat COVID-19, effectively suppressed SARS-CoV-2 infection of PSC-HIOs. In contrast, the histamine-2-blocker famotidine showed no effect. Thus, PSC-HIOs provide an interesting platform to study SARS-CoV-2 infection and to identify or validate drugs.
Food web structure alters ecological communities top-heaviness with little effect on the biodiversity-functioning relationship
Authors: Delmas Eva , Stouffer Daniel B. , Poisot Timothée
Published: June 2020

In a rapidly changing world, the composition, diversity and structure of ecological communities face many threats. Biodiversity-Ecosystem Functioning (BEF) and community food-chain analyses have focused on investigating the consequences of these changes on ecosystem processes and the resulting functions. These different and diverging conceptual frameworks have each produced important results and identified a set of important mechanisms, that shape ecosystem functions. But the disconnection between these frameworks, and the various simplifications of the study systems are not representative of the complexity of real-world communities. Here we use food webs as a more realistic depiction of communities, and use a bioenergetic model to simulate their biomass dynamics and quantify the resulting flows and stocks of biomass. We use tools from food web analysis to investigate how the predictions from BEF and food-chain analyses fit together, how they correlate to food-web structure and how it might help us understand the interplay between various drivers of ecosystem functioning. We show that food web structure is correlated to the community’s efficiency in storing the captured biomass, which may explain the distribution of biomass (top heaviness) across the different trophic compartments (producers, primary and secondary consumers). While we know that ecological network structure is important in shaping ecosystem dynamics, identifying structural attributes important in shaping ecosystem processes and synthesizing how it affects various underpinning mechanisms may help prioritize key conservation targets to protect not only biodiversity but also its structure and the resulting services.
TIP60 acetylates H2AZ and regulates doxorubicin-induced DNA damage sensitivity throughRAD51transcription
Authors: Lee Kwok Kin , Zhang Yanzhou , Tirado- Magallanes Roberto , Rajagopalan Deepa , Bhatia Shreshtha Sailesh , Ng Larry , Desi Ng , Tham Cheng Yong , Teo Wen Shiun , Hoppe Michal Marek , Jeyasekharan Anand D. , Tay Yvonne , Chng Wee Joo , Tenen Daniel G. , Benoukraf Touati , Jha Sudhakar
Published: June 2020

TIP60, a lysine acetyltransferase and H2AZ, a histone H2A variant are involved in transcription and DNA repair. Recent studies suggest that H2AZ acetylation is dependent on TIP60. Here, we show that TIP60 acetylates both isoforms of H2AZin vitroand in cells. Utilizing ChIP-seq and RNA-seq to identify the genes regulated by TIP60-dependent acetylation of H2AZ, we find that TIP60-dependent acetylation of H2AZ correlates with the expression of genes involved in DNA damage repair, amongst several other pathways. In line with this, TIP60-depleted cells exhibit increased sensitivity to the DNA damage-inducing drug doxorubicin. Restoring the expression level ofRAD51, one of the genes involved in the DNA damage repair pathway, partially rescues the doxorubicin sensitivity due to TIP60 depletion. Overall, our study uncovers a role for TIP60 in regulating doxorubicin-induced DNA damage sensitivity in a manner dependent onRAD51transcription.