bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced secondary pollution offset reduction of primary emissions during COVID-19 lockdown in China
Authors: Huang Xin , Ding Aijun , Gao Jian , Zheng Bo , Zhou Derong , Qi Ximeng , Tang Rong , Wang Jiaping , Ren Chuanhua , Nie Wei , Chi Xuguang , Xu Zheng , Chen Liangduo , Li Yuanyuan , Che Fei , Pang Nini , Wang Haikun , Tong Dan , Qin Wei , Cheng Wei , Liu Weijing , Fu Qingyan , Liu Baoxian , Chai Fahe , Davis Steven J , Zhang Qiang , He Kebin
Published: June 2020

To control the spread of the 2019 novel coronavirus (COVID-19), China imposed nationwide restrictions on the movement of its population (lockdown) after the Chinese New Year of 2020, leading to large reductions in economic activities and associated emissions. Despite such large decreases in primary pollution, there were nonetheless several periods of heavy haze pollution in eastern China, raising questions about the well-established relationship between human activities and air quality. Here, using comprehensive measurements and modeling, we show that the haze during the COVID lockdown was driven by enhancements of secondary pollution. In particular, large decreases in NOx emissions from transportation increased ozone and nighttime NO3 radical formation, and these increases in atmospheric oxidizing capacity in turn facilitated the formation of secondary particulate matter. Our results, afforded by the tragic natural experiment of the COVID-19 pandemic, indicate that haze mitigation depends upon a coordinated and balanced strategy for controlling multiple pollutants.
Promoting Protesters’ Compliance: The Effect of General Perceptions of the Police versus Police Actions
Authors: Perry Gali
Published: June 2020

Public willingness to comply with the police is desirable in democratic societies, and even more so in high-risk policing tasks such as protest policing. To allow freedom of speech while maintaining public order, officers require protesters to follow orders and cooperate. The process-based model of policing suggests that protesters’ compliance will be mainly affected by their general perceptions of the police—primarily, trust in the police and perceptions of just policing procedures. In conjunction, police actions during a demonstration and the dynamics between officers and protesters can also affect protesters’ willingness to comply. This study uses a series of Ordinary Least Squares (OLS) regression models to analyse survey responses of 470 protesters who participated in the ‘Occupy’ protests in Israel during 2012. Findings suggest that positive evaluations of trust in the police and policing procedures correlate with compliance; however, when protesters perceived police actions as negative, they were less willing to comply.
Permutational analysis of Saccharomyces cerevisiae regulatory elements
Authors: Dhillon Namrita , Shelansky Robert , Townshend Brent , Jain Miten , Boeger Hinrich , Endy Drew , Kamakaka Rohinton
Published: June 2020

Gene expression in Saccharomyces cerevisiae is regulated at multiple levels. Genomic and epigenomic mapping of transcription factors and chromatin factors has led to the delineation of various modular regulatory elements—enhancers (upstream activating sequences), core promoters, 5′ untranslated regions (5′ UTRs) and transcription terminators/3′ untranslated regions (3′ UTRs). However, only a few of these elements have been tested in combinations with other elements and the functional interactions between the different modular regulatory elements remain under explored. We describe a simple and rapid approach to build a combinatorial library of regulatory elements and have used this library to study 26 different enhancers, core promoters, 5′ UTRs and transcription terminators/3′ UTRs to estimate the contribution of individual regulatory parts in gene expression. Our combinatorial analysis shows that while enhancers initiate gene expression, core promoters modulate the levels of enhancer-mediated expression and can positively or negatively affect expression from even the strongest enhancers. Principal component analysis (PCA) indicates that enhancer and promoter function can be explained by a single principal component while UTR function involves multiple functional components. The PCA also highlights outliers and suggest differences in mechanisms of regulation by individual elements. Our data also identify numerous regulatory cassettes composed of different individual regulatory elements that exhibit equivalent gene expression levels. These data thus provide a catalog of elements that could in future be used in the design of synthetic regulatory circuits.
Polyethylene Oxide Molecular Size Determines the Severity of Atypical Thrombotic Microangiopathy in a Guinea Pig Model of Acute Intravenous Exposure
Authors: Baek Jin Hyen , Shin Hye Kyung H , Koo Soo Min , Gao Yamei , Qu Haiou , Feng Xin , Xu Xiaoming , Pinto Julia , Katneni Upendra , Kimchi-Sarfaty Chava , Buehler Paul W
Published: June 2020

In 2017, Opana ER was voluntarily removed from the U.S. market based on concerns that its risks outweighed its therapeutic benefits. The data that supported this conclusion were based on postmarketing evaluation that demonstrated increased intravenous abuse associated outbreaks of HIV, hepatitis C, and uniquely, a thrombotic thrombocytopenic purpura (TTP)-like syndrome. In 2017, the cause was mechanistically linked to intravenous exposure of the high-molecular weight polyethylene oxide (PEO), an excipient component of the drug product. However, it was unknown how differing PEO preparations might alter this response in vivo. Knowing the likelihood of a PEO driven atypical thrombotic microangiopathy with hemolytic uremic syndrome (TMA-HUS), this study was specifically designed with the primary objective focused on understanding the impact of PEO molecular weight on TMA-HUS in a guinea pig model of acute repeat PEO (1, 4, and 7 MDa) dosing. Results from this analysis suggest that repeated dosing with PEO 4 and 7 MDa, but not 1 MDa induced a marked intravascular hemolysis with schistocytes, mild anemia, thrombocytopenia, hemoglobinuria, and kidney injury, consistent with observations of a TMA-HUS-like syndrome. Nonetheless, observations of tissue microthrombi, complement or altered von Willebrand factor involvement were not observed, which would be consistent with a definitive TMA. Further, only 7 MDa PEO dosing was associated with marked renal hypoxia. Taken together, this study defines renal injury risk with PEO formulations >1 MDa that is driven by a robust intravascular hemolysis and potentially, tissue hypoxia.
The terminalia of the superfamily Scarabaeoidea (Coleoptera): specific glossary, dissecting methodology, techniques and previously unrecorded sexual dimorphism in some difficult groups
Authors: Cristóvão Joana P , Vaz-de-Mello Fernando Z
Published: June 2020

The terminology used for the morphological structures of the abdomen as well as male and female genitalia across the superfamily Scarabaeoidea is discussed, based on a literature review across the group. Issues relating to the orientation of the male terminalia and potential homologies between the ‘genital capsule’- and ‘spiculum gastrale’-bearing taxa are discussed and standardisation of terminology pertaining to some ambiguous terms is proposed. A Scarabaeoidea-specific glossary is presented, and synonyms across the literature are given. Schematic illustrations of the abdomen and terminalia are provided. Some new morphological structures are here described for the first time. A standardised dissection protocol for male and female Scarabaeoidea is proposed. Sexually dimorphic structures in the abdomen of Pleurosticti (Dynastinae, Rutelinae, Melolonthinae and Cetoniinae), Glaphyridae, Phaenomeridinae, Passalidae and Omorgus (Trogidae) are described and illustrated for the first time, providing future workers with the possibility to determine the sex of specimens based on external characters without the need for dissection.
Rapid Detection of Raffaelea lauricola Directly from Host Plant and Beetle Vector Tissues Using Loop-Mediated Isothermal Amplification
Authors: Hamilton Jeffrey L. , Workman J. Noah , Nairn Campbell J. , Fraedrich Stephen W. , Villari Caterina
Published: June 2020

Since its introduction in 2002, laurel wilt disease has devastated indigenous lauraceous species in the southeastern United States. The causal agent is a fungal pathogen, Raffaelea lauricola, which, after being introduced into the xylem of trees by its vector beetle, Xyleborus glabratus, results in a fatal vascular wilt. Rapid detection and accurate diagnosis of infections is paramount to the successful implementation of disease management strategies. Current management operations to prevent the spread of laurel wilt disease are largely delayed by time-consuming laboratory procedures to confirm the diagnosis. In order to greatly speed up the operations, we developed a loop-mediated isothermal amplification (LAMP) species-specific assay that targets the β-tubulin gene region of R. lauricola, and allows for the rapid detection of the pathogen directly from host plant and beetle tissues. The assay is capable of amplifying as little as 0.5 pg of fungal DNA and as few as 50 conidia. The assay is also capable of detecting R. lauricola directly from wood tissue of artificially inoculated redbay saplings as early as 10 and 12 days postinoculation, when testing high-quality and crude DNA extracts, respectively. Finally, crude DNA extracts of individual adult female X. glabratus beetles were assayed and the pathogen was detected from all specimens. This assay greatly reduces the time required to confirm a laurel wilt diagnosis and, because LAMP technology is well suited to provide point-of-care testing, it has the potential to expedite and facilitate implementation of management operations in response to disease outbreaks.
Contamination in Urine Samples Collected Using Bladder Stimulation and Clean Catch Versus Urinary Catheterization in Infants Younger Than 90 Days
Authors: Rivas-García Arístides , Lorente-Romero Jorge , López-Blázquez María , Rodríguez-Jiménez Cristina , Castro-Rodríguez Cristina , Míguez-Navarro María Concepción
Published: June 2020

Objectives

The objective of this study was to compare the risk of contamination for urine samples collected from patients younger than 90 days using 2 different techniques: bladder stimulation and “clean catch” (CC) and urinary catheterization (CATH).

Methods

A case-control study was carried out in the pediatric emergency room of a tertiary hospital between January 2016 and September 2017. All urine samples collected from patients younger than 90 days by CC or CATH were included. The incidence of contaminated urine samples was compared for both methods, and the risk of contamination was estimated using univariate and multivariate analyses.

Results

A total of 473 urine samples were collected, 310 via CATH (65.5%) and 163 via CC (34.5%). The median age was 1.4 months (interquartile range, 0.8–2.1 months), and 54.1% were males. Seventeen patients had a history of urinary tract infection (3.6%), and 16 were diagnosed with a congenital urorenal anomaly (3.4%). Sixteen urine samples were found to be contaminated (3.4%): 5 collected via CATH (1.6%) and 11 via CC (6.8%). The univariate analysis revealed a greater risk of contamination in specimens obtained using CC versus CATH (odds ratio, 4.41; 95% confidence interval, 1.51–12.93), and the multivariate analysis confirmed CC collection as an independent risk factor for contamination (odds ratio, 5.61; 95% confidence interval, 1.83–17.19).

Conclusions

The number of contaminated urine samples in infants younger than 90 days in our pediatric emergency department is low. However, using the CC urine collection technique seems to be an independent risk factor for sample contamination.
Can behaviour impede evolution? Persistence of singing effort after morphological song loss in crickets
Authors: Rayner Jack G. , Schneider Will T. , Bailey Nathan W.
Published: June 2020

Evolutionary loss of sexual signals is widespread. Examining the consequences for behaviours associated with such signals can provide insight into factors promoting or inhibiting trait loss. We tested whether a behavioural component of a sexual trait, male calling effort, has been evolutionary reduced in silent populations of Hawaiian field crickets (Teleogryllus oceanicus).Cricket song requires energetically costly wing movements, but ‘flatwing’ males have feminized wings that preclude song and protect against a lethal, eavesdropping parasitoid. Flatwing males express wing movement patterns associated with singing but, in contrast with normal-wing males, sustained periods of wing movement cannot confer sexual selection benefits and should be subject to strong negative selection. We developed an automated technique to quantify how long males spend expressing wing movements associated with song. We compared calling effort among populations of Hawaiian crickets with differing proportions of silent males and between male morphs. Contrary to expectation, silent populations invested as much in calling effort as non-silent populations. Additionally, flatwing and normal-wing males from the same population did not differ in calling effort. The lack of evolved behavioural adjustment following morphological change in silent Hawaiian crickets illustrates how behaviour might sometimes impede, rather than facilitate, evolution.
Gene swamping alters evolution during range expansions in the protist
Tetrahymena thermophila
Authors: Moerman Felix , Fronhofer Emanuel A. , Wagner Andreas , Altermatt Florian
Published: June 2020

At species’ range edges, individuals often face novel environmental conditions that may limit range expansion until populations adapt. The potential to adapt depends on genetic variation upon which selection can act. However, populations at species’ range edges are often genetically depauperate. One mechanism increasing genetic variation is reshuffling existing variation through sex. Sex, however, can potentially limit adaptation by breaking up existing beneficial allele combinations (recombination load). The gene swamping hypothesis predicts this is specifically the case when populations expand along an abiotic gradient and asymmetric dispersal leads to numerous maladapted dispersers from the range core swamping the range edge. We used the ciliate
Tetrahymena thermophila
as a model for testing the gene swamping hypothesis. We performed replicated range expansions in landscapes with or without a pH-gradient, while simultaneously manipulating the occurrence of gene flow and sexual versus asexual reproduction. We show that sex accelerated evolution of local adaptation in the absence of gene flow, but hindered it in the presence of gene flow. However, sex affected adaptation independently of the pH-gradient, indicating that both abiotic gradients and the biotic gradient in population density lead to gene swamping. Overall, our results show that gene swamping alters adaptation in life-history strategies.
Low and high infection dose transmissions of SARS-CoV-2 in the first COVID-19 clusters in Northern Germany
Authors: Pfefferle Susanne , Günther Thomas , Kobbe Robin , Czech-Sioli Manja , Nörz Dominic , Santer René , Oh Jun , Kluge Stefan , Oestereich Lisa , Peldschus Kersten , Indenbirken Daniela , Huang Jiabin , Grundhoff Adam , Aepfelbacher Martin , Knobloch Johannes K. , Lütgehetmann Marc , Fischer Nicole
Published: June 2020

Objectives

We used viral genomics to deeply analyze the first SARS-CoV-2 infection clusters in the metropolitan region of Hamburg, Germany. Epidemiological analysis and contact tracing together with a thorough investigation of virus variant patterns revealed low and high infection dose transmissions to be involved in transmission events.

Methods

Infection control measures were applied to follow up contract tracing. Metagenomic RNA- and SARS-CoV-2 amplicon sequencing was performed from 25 clinical samples for sequence analysis and variant calling.

Results

The index patient acquired SARS-CoV-2 in Italy and after his return to Hamburg transmitted it to 2 out of 132 contacts. Virus genomics and variant pattern clearly confirms the initial local cluster. We identify frequent single nucleotide polymorphisms at positions 241, 3037, 14408, 23403 and 28881 previously described in Italian sequences and now considered as one major genotype in Europe. While the index patient showed a single nucleotide polymorphism only one variant was transmitted to the recipients. Different to the initial cluster, we observed in household clusters occurring at the time in Hamburg also intra-host viral species transmission events.

Conclusions

SARS-CoV-2 variant tracing highlights both, low infection dose transmissions suggestive of fomites as route of infection in the initial cluster and high and low infection dose transmissions in family clusters indicative of fomites and droplets as infection routes. This suggests (1) single viral particle infection can be sufficient to initiate SARS-CoV-2 infection and (2) household/family members are exposed to high virus loads and therefore have a high risk to acquire SARS-CoV-2.
CyTOF analysis identifies unusual immune cells in urine of BCG-treated bladder cancer patients
Authors: Castellano Eva , Samba Célia , Esteso Gloria , Simpson Laura , Vendrame Elena , García-Cuesta Eva M. , López-Cobo Sheila , Álvarez-Maestro Mario , Linares Ana , Leibar Asier , Ranganath Thanmayi , Reyburn Hugh T. , Martínez-Piñeiro Luis , Blish Catherine , Valés-Gómez Mar
Published: June 2020

High grade non-muscle-invasive bladder tumours are treated with transurethral resection followed by recurrent intravesical instillations of Bacillus Calmette Guérin (BCG). Although bladder cancer patients respond well to BCG, important questions remain unanswered, including how to identify at early stages non-responder patients and patients at risk to abandon the treatment. Here, we analysed the cells released into the urine of bladder cancer patients longitudinally 3-7 days after BCG instillations. Mass cytometry (CyTOF) analyses revealed that most cells were granulocytes and monocytes rather than effector lymphocytes, and most expressed activation markers. A novel population of CD15+CD66b+CD14+CD16+cells was very abundant in several samples and expression of these markers was confirmed using flow cytometry and qPCR. Samples of patients with a stronger inflammatory response contained more cells in urine; however, this was not due to haematuria, as the proportions of the cell populations observed were different from blood. We provide the proof-of-concept for a new approach to analyse samples that may help classify patients and identify those at risk of BCG infection and other unwanted BCG-related events.
Evaluation of SARS-CoV-2 in Breastmilk from 18 Infected Women
Authors: Chambers Christina D. , Krogstad Paul , Bertrand Kerri , Contreras Deisy , Tobin Nicole H. , Bode Lars , Aldrovandi Grace M.
Published: June 2020

To The Editor

Currently, the U.S. Centers for Disease Control and Prevention, American Academy of Pediatrics and the World Health Organization advise that women who are infected with SARS-CoV-2 may choose to breastfeed with appropriate protections to prevent transmission of the virus through respiratory droplets.(1) However, the potential for exposure to SARS-CoV-2 through breastfeeding is currently unknown. To date, case reports on breastmilk samples from a total of 24 SARS-CoV-2-infected women have been published.(2-7) Of those, viral RNA was detected in ten breastmilk samples from four women. In some but not all cases, environmental contamination as the source of the virus or retrograde flow from an infected infant could not be ruled out.
Light propagation within N95 Filtered Face Respirators: A simulation study for UVC decontamination
Authors: Lilge Lothar , Manalac Angelica , Weersink Madrigal , Schwiegelshohn Fynn , Young-Schultz Tanner , Abdalrhman Abdallatif Satti , Wang Chengjin , Ngan Aldrich , Gu Frank X. , Betz Vaughn , Hofmann Ron
Published: June 2020

This study presents numerical simulations of UVC light propagation through seven different filtered face respirators (FFR) to determine their suitability for UV germicidal inactivation (UVGI). UV propagation was modelled using the FullMonte program for two external light illuminations. The optical properties of the dominant three layers were determined using the inverse adding doubling method.

The resulting fluence rate volume histograms and the lowest fluence rate recorded in the modelled volume, sometimes in the nW cm-2, provide feedback on a respirator’s suitability for UVGI and the required exposure time for a given light source. While UVGI can present an economical approach to extend an FFR’s useable lifetime, it requires careful optimization of the illumination setup and selection of appropriate respirators.

Abstract Figure
Study of pre-hospital care of Out of Hospital Cardiac Arrest victims and their outcome in a tertiary care hospital in India
Authors: Bhat Rachana , Ravindra Prithvishree , Sahu Ankit Kumar , Mathew Roshan , Wilson William
Published: June 2020

BACKGROUND

India does not have a formal cardiac arrest registry and a centralized emergency medical system. In this study, we aimed to assess the prehospital care received by the patients with OHCA and to predict the factors that could influence their outcome.

METHODS

We performed a prospective observational study, including OHCA patients presenting to the emergency department (ED) between February 2019 and January 2020. A structured proforma was used to capture information like basic demography, prehospital details like bystander cardiopulmonary resuscitation (CPR), use of an automated external defibrillator (AED), clinical profile, and outcome.

RESULTS

Among the included 205 patients, the majority were male (71.2%) and belonged to older age (49.3%). The nature of arrest was predominantly non-traumatic (82.4%). The initial rhythm at presentation was non-shockable (96.5%). Return of spontaneous circulation (ROSC) was achieved in 17 (8.3%) patients, of which only 3 (1.4%) patients survived till discharge. The home was the most common location of OHCA (116, 56.6%). Among the OHCA patients, witnessed arrests were seen only in 64 (31.2%), of which 15 (7.8%) received bystander CPR, and AED was used in 1% of the patients. The initial shockable rhythm was a significant predictor of ROSC (OR 18.97 95%CI 3.83-93.89; p<0.001) and survival to discharge (OR 42.67; 95%CI 7.69-234.32; p<0.001).

CONCLUSION

In a developing country like India, this study underlines the poor status of the prehospital system like lower bystander CPR, AED and ambulance usage. Moreover, ROSC was seen only in less than 10% of patients, and only 1.3% got discharged from the hospital.
Genetic determinants of daytime napping and effects on cardiometabolic health
Authors: Dashti Hassan S. , Daghlas Iyas , Lane Jacqueline M. , Huang Yunru , Udler Miriam S. , Wang Heming , Ollila Hanna M. , Jones Samuel E. , Kim Jaegil , Wood Andrew R. ,   23andMe Research Team, Weedon Michael N. , Aslibekyan Stella , Garaulet Marta , Saxena Richa
Published: June 2020

Daytime napping is a common, heritable behavior, but its genetic basis and causal relationship with cardiometabolic health remains unclear. Here, we performed a genome-wide association study of self-reported daytime napping in the UK Biobank (n=452,633) and identified 123 loci of which 60 replicated in 23andMe research participants (n=541,333). Findings included missense variants in established drug targets (HCRTR1, HCRTR2), genes with roles in arousal (TRPC6, PNOC), and genes suggesting an obesity-hypersomnolence pathway (PNOC, PATJ). Signals were concordant with accelerometer-measured daytime inactivity duration and 33 signals colocalized with signals for other sleep phenotypes. Cluster analysis identified 3 clusters suggesting distinct nap-promoting mechanisms with heterogeneous associations with cardiometabolic outcomes. Mendelian randomization showed potential causal links between more frequent daytime napping and higher systolic blood pressure, diastolic blood pressure, and waist circumference.
Guillain-Barr é syndrome in COVID-19: A scoping review
Authors: Ahmad Imran , Rathore Farooq Azam
Published: June 2020

Introduction

The novel corona virus (COVID19) can result in several neurological complications. Guillain-Barré Syndrome (GBS) is one of them and has been reported from different parts of the world in this pandemic. It is an acute post infectious polyneuropathy. The review aims to summarize the demographic features, clinical presentation, diagnostics workup, and management strategies of COVID-19 associated GBS reported in literature.

Material and method

We searched Medline, PubMed Central, SCOPUS and Google Scholar using pre-defined keywords, with no time limits and in English language only. We aimed to include all kind of manuscripts. Last search was done on 18th May 2020.

Demographics, clinical features, diagnostic workup, management, and outcomes were documented in the data sheet.

Results

We identified 24 cases of COVID-19 associated GBS. Most of the cases were reported from Italy followed by USA. Majority were males (18 /24) The age ranged from 23 -84 years. The clinical presentation was typical sensory-motor GBS in most. Nine patients had facial palsy of which five had bilateral involvement. Two patients had bilateral abducent nerve palsy while two presented as paraparetic GBS variant with autonomic dysfunction. Electrodiagnostics was performed in 17 patients only and 12 had typical features of acute inflammatory demyelinating polyneuropathy.. Intravenous immunoglobulins were the preferred mode of treatment in most of the patient. There was one death, and most were discharged to rehabilitation or home.

Conclusion

GBS is a frequent neurological complication associated with COVID-19. There is no clear causative relationship between GBS, and COVID-19 at present and more data are needed to establish the casualty. However, most cases have a post-infectious onset with male preponderance. Most of the cases have a typical presentation but some may present in an atypical way. Prognosis is generally good.
Risk and severity of COVID-19 and ABO blood group in transcatheter aortic valve patients
Authors: Kibler Marion , Carmona Adrien , Marchandot Benjamin , Matsushita Kensuke , Trimaille Antonin , Kanso Mohamad , Dietrich Laurent , How-Choong Cécile , Odier Albane , Gennesseaux Gabrielle , Schramm Ophélie , Reydel Antje , Kindo Michel , Hoang Minh , Hess Sébastien , Sato Chisato , Caillard Sophie , Jesel Laurence , Morel Olivier , Ohlmann Patrick
Published: June 2020

Background

Although cardiovascular disease has been associated with an increased risk of coronavirus disease 2019 (COVID-19), no studies have reported its clinical course in patients with aortic stenosis who had undergone transcatheter aortic valve replacement (TAVR).

Several observational studies have found an association between the A blood group and an increased susceptibility to SARS-CoV-2 infection, whereas the O blood group appears to be protective.

Objective

To investigate the frequency and clinical course of COVID-19 in a large sample of patients who had undergone TAVR and to determine the associations of the ABO blood group with disease occurrence and outcomes.

Methods

Patients who had undergone TAVR between 2010 and 2019 were included in this study and followed-up through the recent COVID-19 outbreak. The main outcomes were the occurrence and severity (hospitalization and/or death) of COVID-19 and their association with the ABO blood group.

Results

Of the 1125 patients who had undergone TAVR, 403 (36%) died before January 1, 2020, and 20 (1.8%) were lost to follow-up. The study sample therefore consisted of 702 patients. Among them, we identified 22 cases (3.1%) with COVID-19. Fourteen patients (63.6%) were hospitalized or died of disease. Multivariate analysis identified the A blood group (versus others) as the only independent predictor of COVID-19 in patients who had undergone TAVR (odds ratio [OR] = 6.32; 95% confidence interval [CI] = 2.11-18.92; p=0.001). The A blood group (versus others; OR = 8.27; 95% CI = 1.83-37.43, p=0.006) and a history of cancer (OR = 4.99; 95% CI = 1.64-15.27, p = 0.005) were significantly and independently associated with disease severity (hospitalization and/or death).

Conclusions

Patients who had undergone TAVR are vulnerable to COVID-19. The subgroup with the A blood group was especially prone to develop the disease and showed unfavorable outcomes.

Condensed abstract

Among 702 patients who had undergone TAVR between 2010 and 2019 and who were alive on January 1, 2020, 22 patients developed COVID-19. Fourteen patients (63.6%) were hospitalized or died of disease. The A blood group (versus others) was the only independent predictor of COVID-19. The A blood group and a history of cancer were significantly and independently associated with disease severity (hospitalization and/or death). Altogether these findings suggest that patients who had undergone TAVR are vulnerable to COVID-19. The subgroup with the A blood group was especially prone to develop the disease and showed unfavorable outcomes.
Impact of social distancing measures for preventing coronavirus disease 2019 [COVID-19]: A systematic review and meta-analysis protocol
Authors: Regmi Krishna , Lwin Cho Mar
Published: June 2020

Introduction

Social distancing measures (SDMs) protect public health from the outbreak of coronavirus disease 2019 (COVID-19). However, the impact of SDMs has been inconsistent and unclear. This study aims to assess the effects of SDMs (e.g. isolation, quarantine) for reducing the transmission of COVID-19.

Methods and analysis

We will conduct a systematic review meta-analysis research of both randomised controlled trials and non-randomised controlled trials. We will search MEDLINE, EMBASE, Allied & Complementary Medicine, COVID-19 Research and WHO database on COVID-19 for primary studies assessing the effects of SDMs (e.g. isolation, quarantine) for reducing the transmission of COVID-19, and will be reported in accordance with PRISMA statement. The PRISMA-P checklist will be used while preparing this protocol. We will use Joanna Briggs Institute guidelines (JBI Critical Appraisal Checklists) to assess the methodological qualities and synthesised performing thematic analysis. Two reviewers will independently screen the papers and extracted data. If sufficient data are available, the random-effects model for meta-analysis will be performed to measure the effect size of SDMs or the strengths of relationships. To assess the heterogeneity of effects, I2together with the observed effects (Q-value, with degrees of freedom) will be used to provide the true effects in the analysis.

Ethics and dissemination

Ethics approval and consent will not be required for this systematic review of the literature as it does not involve human participation. We will be able to disseminate the study findings using the following strategies: we will be publishing at least one paper in peer-reviewed journals, and an abstract will be presented at suitable national/international conferences or workshops. We will also share important information with public health authorities as well as with the World Health Organization. In addition, we may post the submitted manuscript under review to bioRxiv, medRxiv, or other relevant pre-print servers.

Strengths and limitations of this study

To our knowledge, this study will be the first systematic review to examine the impact of social distancing measures to reduce transmission of COVID-19.

This study will offer highest level of evidence for informed decisions, drawing a broader framework.

This protocol reduces the possibility of duplication, provides transparency to the methods and procedures that will be used, minimise potential biases and allows peer-review.

This research is not externally funded, and therefore time and resource will be constrained.

If included studies will be variable in sample size, quality and population, which may open to bias, and the heterogeneity of data will preclude a meaningful meta-analysis to measure the impact of specific SDMs
COVID-19: a crash test for biomedical publishing?
Authors: Iourov Ivan Y , Zelenova Maria A , Vorsanova Svetlana G
Published: June 2020

The effect of COVID-19 on biomedical publishing (BP) (i.e. scientific biomedical periodicals continuously published by research communities or commercial publishers) has not been deeply explored. To estimate the immediate COVID-19 impact on BP, we have assessed PubMed-indexed articles about COVID-19 (PMIAC) from December 2019 to April 2020. PMIAC have been classified according to publication date, country, and journals for evaluation of time-, region- and scientometric-dependant impact of COVID-19 on BP and have been curated manually (i.e. each entry has been individually analyzed). PMIAC analysis reflects geographic and temporal parameters of outbreak spread. A major BP problem is related to the fact that only 40% of articles report/review/analyze data. Another BP weakness is the clusterization of “highly-trusted” publications according to countries of origin and “highly impacting” journals. Finally, a problem highlighted by COVID-19 crisis is the increased specification of biomedical research. To solve the problem, analytical reviews integrating data from different areas of biology and medicine are required. The data on PMIAC suggest priority of “what is published” over “where it is published” and “who are the authors”. We believe that our brief analysis may help to shape forthcoming BP to become more effective in solving immediate problems resulted from global threats.
Seroprevalence against COVID-19 and follow-up of suspected cases in primary health care in Spain
Authors: Brotons C , Serrano J , Fernández D , Garcia-Ramos C , Ichazo B , Lemaire J , Montenegro P , Moral I , Pérez Wienese R , Pitarch M , Puig M , Vilella MT , Sellarès J
Published: June 2020

Background

During the coronavirus disease 2019 (COVID-19) pandemic little information has been available about patients with mild or moderate symptoms attended and followed in the primary care setting, most of whom had an unknown status for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Objectives

We aim to measure the seroprevalence of antibodies against SARS-CoV-2 infection in a community sample of asymptomatic individuals and among symptomatic patients (without confirmed diagnosis) followed in a primary care setting.

As a secondary objective, we estimated the proportions of symptomatic patients seeing at an emergency department (ED), hospitalized or dying, and identified the most important clinical symptoms associated with a positive infection.

Methods

From April 21 to April 24 2020, we selected a random sample of 600 individuals stratified by age groups, from a total population of 19,899 individuals from a community area in Barcelona (study population 1). From April 29 to May 5 2020, we also invited all the patients that had been followed by general practitioners (GPs) (study population 2).

We used for both populations COVID-19 Rapid lateral flow immunoassay which qualitatively assesses the presence of patient-generated IgG and IgM in approximately 10-15 minutes.

The prevalence (95% confidence intervals [CI]) of infection (past and current) was defined as the proportion of individuals with antibody seropositivity. Odds ratios (ORs) for a positive test result were estimated using logistic regression analysis.

Results

Three hundred and eleven asymptomatic individuals from the randomly selected sample accepted to participate in the study. The overall mean age was 43.7 years (SD 21.79, range 1-94) and 55% were women. Seventeen individuals were seropositive for IgM and/or IgG, resulting an overall prevalence of 5,47% (95% CI, 3.44-8.58).

Six-hundred and thirty-four symptomatic patients were followed by GPs. The overall mean age was 46.97 years (SD 20.05, range 0-92) and 57.73% were women. Of these, 244 patients (38.49%) were seropositive for IgM and/or IgG.

During the follow-up period, 27.13% of symptomatic patients attended the ED, 11.83% were hospitalized and about 2% died.

Results of the multivariate logistic regression analysis showed that the OR for a positive test was significantly increased in patients who had fever (>38°C), ageusia and contact with a patient diagnosed with COVID-19.

Conclusions

The seroprevalence of antibodies against SARS-CoV-2 among asymptomatic individuals in the general population was lower than expected.

Approximately 40% of the symptomatic patients followed by GPs during the peak months of the pandemic in Barcelona, were positive. Fever (>38°C), anosmia, ageusia and contact with a patient diagnosed with COVID-19 were associated with a positive test result.
A plasma membrane nanoplatform ensures signal specificity during osmotic signaling in plants
Authors: Smokvarska M. , Francis C. , Platre M.P. , Fiche J.B. , Alcon C. , Dumont X. , Nacry P. , Bayle V. , Nollmann M. , Maurel C. , Jaillais Y. , Martiniere A.
Published: June 2020

In the course of their growth and development plants have to constantly perceive and react to their environment. This is achieved in cells, by the coordination of complex combinatorial signaling networks. However, how signal integration and specificity are achieved in this context is unknown. With a focus on the hyperosmotic stimulus, we use live super-resolution light imaging methods to demonstrate that a Rho GTPase, Rho-of-Plant 6 (ROP6), forms stimuli-dependant nanodomains within the PM. These nanodomains are necessary and sufficient to transduce production of reactive oxygen species (ROS),that act as secondary messengers and trigger several plant adaptive responses to osmotic constraints. Furthermore, ROP6 activation triggers the nanoclustering of two NADPH oxidases that subsequently generates ROS. ROP6 nanoclustering is also needed for cell surface auxin signaling, but short-time auxin treatment does not induce ROS accumulation. We show that auxin-induced ROP6 nanodomains, unlike osmotically-driven ROP6 clusters, do not recruit the NADPH oxidase, RBOHD. Together, our results suggest that Rho GTPase nano-partitioning at the PM ensure signal specificity downstream of independent stimuli.
Improving qBOLD based measures of oxygen extraction fraction using hyperoxia-BOLD derived measures of blood volume
Authors: Stone Alan J , Blockley Nicholas P
Published: June 2020

Purpose

Streamlined-qBOLD (sqBOLD) is a refinement of the quantitative BOLD (qBOLD) technique capable of producing non-invasive and quantitative maps of oxygen extraction fraction (OEF) in a clinically feasible scan time. However, sqBOLD measurements of OEF have been reported as being systematically lower than expected in healthy brain. Since the qBOLD framework infers OEF from the ratio of the reversible transverse relaxation rate (R2′) and deoxygenated blood volume (DBV), this underestimation has been attributed the overestimation of DBV. Therefore, this study proposes the use of an independent measure of DBV using hyperoxia-BOLD and investigates whether this results in improved estimates of OEF.

Methods

Monte Carlo simulations were used to simulate the qBOLD and hyperoxia-BOLD signals and to compare the systematic and noise related errors of sqBOLD and the new hyperoxia-qBOLD (hqBOLD) technique. Experimentally, sqBOLD and hqBOLD measurements were performed and compared with TRUST (T2relaxation under spin tagging) based oximetry in the sagittal sinus.

Results

Simulations showed a large improvement in the uncertainty of DBV measurements leading to a much improved dynamic range for OEF measurements with hqBOLD. In a group of ten healthy volunteers, hqBOLD produced measurements of OEF in cortical grey matter (OEFhqBOLD= 38.1 ± 10.1 %) that were not significantly different to TRUST oximetry measures (OEFTRUST= 40.4 ± 7.7 %), whilst sqBOLD derived measures (OEFsqBOLD= 16.1 ± 3.1 %) were found to be significantly different.

Conclusion

The simulations and experiments in this study demonstrate that an independent measure of DBV provides improved estimates of OEF.
Addressing differentiation in live human keratinocytes by assessment of membrane packing order
Authors: Gutowska-Owsiak Danuta , Eggeling Christian , Ogg Graham S , de la Serna Jorge Bernardino
Published: June 2020

Differentiation of keratinocytes is critical for epidermal stratification and formation of a protective stratum corneum. It involves a series of complex processes leading through gradual changes in characteristics and functions of keratinocytes up to their programmed cell death via cornification. The stratum corneum is an impermeable barrier, comprised of dead cell remnants (corneocytes) embedded within lipid matrix. Corneocyte membranes are comprised of specialized lipids linked to late differentiation proteins, contributing to the formation of a highly stiff and mechanically strengthen layer. To date, the assessment of the progression of keratinocyte differentiation is only possible by determination of specific differentiation markers, e.g. by using proteomics-based approaches. Unfortunately, this requires fixation or cell lysis, and currently there is no robust methodology available to study differentiation in living cells, neither at a single cell, nor in high throughput. Here, we explore a new live-cell based approaches for screening differentiation advancement in keratinocytes, in a “calcium switch” model. We employ a polarity-sensitive dye, Laurdan, and Laurdan general polarization function (GP) as a reporter of the degree of membrane lateral packing order or condensation, as an adequate marker of differentiation. We show that the assay is straightforward and can be conducted either on a single cell level using confocal spectral imaging or on the ensemble level using a fluorescence plate reader. Such systematic quantification may become useful for understanding mechanisms of keratinocyte differentiation, such as the role of membrane inhomogeneities in stiffness, and for future therapeutic development.
The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types
Authors: Daniloski Zharko , Jordan Tristan X. , Ilmain Juliana K. , Guo Xinyi , Bhabha Gira , tenOever Benjamin R. , Sanjana Neville E.
Published: June 2020

A novel isolate of the SARS-CoV-2 virus carrying a point mutation in the Spike protein (D614G) has recently emerged and rapidly surpassed others in prevalence. This mutation is in linkage disequilibrium with an ORF1b protein variant (P314L), making it difficult to discern the functional significance of the Spike D614G mutation from population genetics alone. Here, we perform site-directed mutagenesis to introduce the D614G variant and show that in multiple cell lines, including human lung epithelial cells, that the D614G mutation is up to 8-fold more effective at transducing cells than wild-type. We demonstrate increased infection using both Spike-pseudotyped lentivirus and intact SARS-CoV-2 virus. Although there is minimal difference in ACE2 receptor binding between the Spike variants, we show that the G614 variant is more resistant to proteolytic cleavagein vitroand in human cells, suggesting a possible mechanism for the increased transduction. This result has important implications for the efficacy of Spike-based vaccines currently under development in protecting against this recent and highly-prevalent SARS-CoV-2 isolate.
Altered structure and dynamics of pathogenic cytochrome c variants correlate with increased apoptotic activity
Authors: Fellner Matthias , Parakra Rinky , McDonald Kirstin O. , Kass Itamar , Jameson Guy N.L. , Wilbanks Sigurd M. , Ledgerwood Elizabeth C.
Published: June 2020

Mutation of cytochromecin humans causes mild autosomal dominant thrombocytopenia. The role of cytochromecin platelet formation, and molecular mechanism underlying the association of cytochromecmutations with thrombocytopenia remains unknown, although a gain-of-function is most likely. Cytochromeccontributes to several cellular processes, with exchange between conformational states proposed to regulate changes in function. Here we use experimental and computational approaches to determine whether pathogenic variants share changes in structure and function, and to understand how these changes might occur. We find that three pathogenic variants (G41S, Y48H, A51V) cause an increase in apoptosome activation and peroxidase activity. Molecular dynamics simulations of these variants, and two non-naturally occurring variants (G41A, G41T), indicate that increased apoptosome activation correlates with increased overall flexibility of cytochromec, particularly movement of the Ω loops. This suggests that the binding of cytochromecto apoptotic protease activating factor-1 (Apaf-1) may involve an “induced fit” mechanism which is enhanced in the more conformationally mobile variants. In contrast, peroxidase activity did not significantly correlate with protein dynamics suggesting that the mechanism by which the variants alter peroxidase activity is not related to the conformation dynamics of the hexacoordinate heme Fe state of cytochromecanalyzed in the simulations. Recent suggestions that conformational mobility of specific regions of cytochromecunderpins changes in reduction potential and the alkaline transition pKwere not supported. These data highlight that conformational dynamics of cytochromecdrives some but not all of its properties and activities.
Integrated analysis of high throughput transcriptomic data revealed specific gene expression signature of cardiomyocytes
Authors: Omrani Mohammad Reza , Sharifi Erfan , Khazaei Niusha , Esfahani Sahel Jahangiri , Kieran Nicholas W. , Hashemi Hadi , Mohammadnia Abdulshakour , Yaqubi Moein
Published: June 2020

Acquiring a specific transcriptomic signature of the human and mouse cardiomyocyte (CM) will greatly increase our understanding of their biology and associated diseases that remain the most deadly across the world. In this study, using comprehensive transcriptomic mining of 91 cell types over 877 samples from bulk RNA-sequencing, single cell RNA-sequencing, and microarray techniques, we describe a unique 118-gene signature of human and mouse primary CMs. Once we had access to this CM-specific gene signature, we investigated the spatial heterogeneity of CMs throughout the heart tissue. Moreover, we compared the CM-specific gene signature to that of CMs derived from 10 differentiation protocols, and we identified the protocols that generate cells most similar to primary CMs. Finally, we looked at the specific differences between primary and differentiated CMs and found that differentiated cells underexpress genes related to CM development and maturity. The differentiated cells conversely overexpressed cell cycle-related genes, resulting in the progenitor features that remain in differentiated CMs compared to primary adult CMs. The presence of histone post translational modification H3K27ac from ChIP sequencing data sets were used to confirm transcriptomic findings. To the best of our knowledge, this is the most comprehensive study to date that unravels the unique transcriptomic signature of primary and differentiated CMs. This study provides important insights into our understanding of CM biology and the molecular mechanisms that make them such a unique cell type. Moreover, the specific transcriptomic signature of CMs could be used in developmental studies, stem cell therapy, regenerative medicine, and drug screening assays.