bluuebunny/crossref_metadata_2025 huggingface dataset:
Would India Really Touch the Peak of SARS COVID 19 Cases or Deaths in Near Future?
Authors: Gupta Pramod K.
Published: May 2020

Background

The Government, Health System and even an individual citizen of India is alarmed expecting the height of pandemic of SARS-COVID-19 in near future. Many experts worldwide predict it to happen in India between end of May and end of July.

Objectives

The aim of this research was to find an answer that whether India would come across the looming conditions of SARS-COVID-19 in coming days given the prevailing circumstances so far.

Methods

The proposed approach used fundamental concept of Statistics by fixing the standard reference to the number of daily new tests conducted by a country. We thus computed the percentage of daily new cases and daily new deaths, in using such references. The trends were studied using simple line chart. The theory of three sigma was also used to build the upper bound for daily new cases and deaths, specifically for India to see the extreme conditions.

Results

The analysis was done using data from January to till May 18, 2020 for India, Italy, USA and UK. The trend of India was almost fix between ~2% to ~6% till May 18, 2020. On contrary, Italy, USA and UK were touched the Peak on March 29, 2020 (24.38%), April 26, 2020 (23.51%) and April 24, 2020 (24.91%), respectively and declining since then. Similar trends were also noted in daily new deaths, except Italy.

Conclusions

The proposed new concept for fixing universal reference provides a consistent and coherent results. It is thus clear from observed data so far that India is not going to encounter the frightened conditions or peak, like, Italy, USA, and UK for pandemic SARS-COVID-19, given the existing conditions, excluding the current migration.
Visual information routes in the posterior dorsal and ventral face network studied with intracranial neurophysiology, and white matter tract endpoints
Authors: Babo-Rebelo M , Puce A , Bullock D , Hugueville L , Pestilli F , Adam C , Lehongre K , Lambrecq V , Dinkelacker V , George N
Published: May 2020

Occipito-temporal regions within the face network process perceptual and socio-emotional information, but the dynamics and information flow between different nodes of this network is still debated. Here, we analyzed intracerebral EEG from 11 epileptic patients viewing a stimulus sequence beginning with a neutral face with direct gaze. The gaze could avert or remain direct, while the emotion changed to fearful or happy. N200 field potential peak latencies indicated that face processing begins in inferior occipital cortex and proceeds anteroventrally to fusiform and inferior temporal cortices, in parallel. The superior temporal sulcus responded preferentially to gaze changes with augmented field potential amplitudes for averted versus direct gaze, and large effect sizes relative to other network regions. An overlap analysis of posterior white matter tractography endpoints (from 1066 healthy brains) relative to active intracerebral electrodes in the 11 patients showed likely involvement of both dorsal and ventral posterior white matter pathways. Overall, our data provide new insight on the timing of face and social cue processing in the occipito-temporal brain and anchor the superior temporal cortex in dynamic gaze processing.
Protocol for analysis of glycoproteomics LC-MS data using GlycReSoft
Authors: Klein Joshua A. , Zaia Joseph
Published: May 2020

Summary/Abstract

The GlycReSoft software tool allows users to process glycoproteomics LC-MS data sets. The tool accepts proteomics database search results or a user-defined list of proteins in the sample. GlycReSoft processes LC-MS data to yield deconvoluted exact mass values. The user has the option to import a list of theoretical glycans from an external database, a curated glycan list, or a measured glycome. The tool assembles a list of theoretical glycopeptides from the lists of theoretical glycans and proteins, respectively. The program then scores the tandem mass spectra in the LC-MS data files and provides graphical views of the identified glycopeptides for each protein in the sample, and the set of glycoforms identified for each peptide sequence.
Assessment of NR4A Ligands that Directly Bind and Modulate the Orphan Nuclear Receptor Nurr1
Authors: Munoz-Tello Paola , Lin Hua , Khan Pasha , de Vera Ian Mitchelle S. , Kamenecka Theodore M. , Kojetin Douglas J.
Published: May 2020

Nurr1/NR4A2 is an orphan nuclear receptor transcription factor implicated as a potential drug target for neurological disorders including Alzheimer’s and Parkinson’s diseases. Previous studies identified small molecule modulators of NR4A nuclear receptors including Nurr1 and Nur77/NR4A1; it remains unclear whether these ligands affect Nurr1 through direct binding or indirect non-binding mechanisms. We assessed a panel of twelve ligands reported to affect NR4A activity for Nurr1-dependent and Nurr1-independent transcriptional effects and binding to the Nurr1 ligand-binding domain (LBD). Most of the NR4A ligands show Nurr1-independent effects on transcription in a cell type-specific manner, suggesting they may function through binding to effector proteins whose downstream activities influence Nurr1 function. Protein NMR spectroscopy structural footprinting data show that 4-amino-7-chloroquinoline derivatives (amodiaquine and chloroquine) and cytosporone B directly bind the Nurr1 LBD. In contrast, other NR4A ligands including commercially available compounds such as C-DIM12, celastrol, camptothecin, IP7e, isoalantolactone, and TMPA do not bind the Nurr1 LBD. Interestingly, previous crystal structures indicate that cytosporone B analogs bind to surface pockets in the Nur77 LBD, but protein NMR data indicate cytosporone B likely binds to the Nurr1 orthosteric pocket. These findings should influence medicinal chemistry efforts that desire to optimize Nurr1-binding ligands as opposed to ligands that function through binding to Nurr1 effector proteins.
Coupling transcriptomics and behaviour to unveil the olfactory system ofSpodoptera exigualarvae
Authors: Llopis-Giménez Angel , Carrasco-Oltra Tamara , Jacquin-Joly Emmanuelle , Herrero Salvador , Crava Cristina M.
Published: May 2020

Chemoreception in insects is crucial for many aspects related to food seeking, enemy avoidance, and reproduction. Different families of receptors and binding proteins interact with chemical stimuli, including odorant receptors (ORs), ionotropic receptors (IRs), gustatory receptors (GRs), odorant binding proteins (OBPs) and chemosensory proteins (CSPs). In this work, we describe the chemosensory-related gene repertoire of the worldwide spread pestSpodoptera exigua(Lepidoptera: Noctuide) focusing on the transcripts expressed in larvae, which feed on many horticultural crops producing yield losses. A comprehensivede novoassembly that includes reads from chemosensory organs of larvae and adults, and other larval tissues, enabled us to annotate 200 candidate chemosensory-related genes encoding 63 ORs, 28 IRs, 38 GRs, 48 OBPs and 23 CSPs. Of them, 51 transcripts are new annotations. RNA-seq and reverse transcription PCR analyses show that 50 ORs are expressed in larval heads, and 15 OBPs are larva-specific. To identify candidate ecologically-relevant odours forS. exigualarvae, we set up behavioural experiments with different volatile organic compounds (VOCs). 1-hexanol triggers attraction at the three timepoints tested and linalool repels larvae at any timepoints. Other five VOCs elicit behavioural response at single timepoint. Lastly, we tested if pre-exposure to single VOCs influence the expression patterns of selected ORs and pheromone binding proteins (PBPs), showing a massive and general up-regulation of some ORs after 24h exposure. This work sets the basis for the study of chemosensation inS. exigualarvae, boosting further studies aimed to characterize chemosensory-related genes that underlie ecologically-relevant behaviours of larval stage.
Adaptation of utility functions to reward distribution in rhesus monkeys
Authors: Bujold Philipe M. , Ferrari-Toniolo Simone , Schultz Wolfram
Published: May 2020

This study investigated the influence of experienced reward distributions on the shape of utility functions inferred from economic choice. Utility is the hypothetical variable that appears to be maximized by the choice. Despite the generally accepted notion that utility functions are not insensitive to external references, the exact occurrence of such changes remains largely unknown. Here we benefitted from the capacity to perform thorough and extensive experimental tests of one of our evolutionary closest, experimentally viable and intuitively understandable species, the rhesus macaque monkey. Data from thousands of binary choices demonstrated that the animals’ preferences changed dependent on the statistics of recently experienced rewards and adapted to future expected rewards. The elicited utility functions shifted and extended their shape with several months of changes in the mean and range of reward distributions. However, the adaptations were usually not complete, suggesting that past experiences remained present when anticipating future rewards. Through modelling, we found that reinforcement learning provided a strong basis for explaining these adaptations. Thus, rather than having stable and fixed preferences assumed by normative economic models, rhesus macaques flexibly shaped their preferences to optimize decision-making according to the statistics of the environment.
Intrinsic ecological dynamics drive biodiversity turnover in model metacommunities
Authors: O’Sullivan Jacob D. , Terry J. Christopher D. , Rossberg Axel G.
Published: May 2020

Turnover of species composition through time is frequently observed in ecosystems. It is often interpreted as indicating the impact of changes in the environment. Continuous turnover due solely to ecological dynamics—species interactions and dispersal—is also known to be theoretically possible, however the prevalence of such autonomous turnover in natural communities remains unclear. Here we demonstrate that observed patterns of compositional turnover and other important macroecological phenomena can be reproduced in large spatially explicit model ecosystems, without external forcing such as environmental change or the invasion of new species into the model. These results imply that the potential role of autonomous turnover as a widespread and important natural process is underappreciated, challenging assumptions implicit in many observation and management tools. Quantifying the baseline level of compositional change would greatly improve ecological status assessments.

One Sentence Summary

Biodiversity change previously attributed to external drivers is explainable as resulting from intrinsic ecosystem dynamics.
Children cooperate more successfully with non-kin than with siblings
Authors: Barragan-Jason Gladys , Cauchoix Maxime , Regnier Anne , Bourjade Marie , Hopfensitz Astrid , Chaine Alexis S.
Published: May 2020

Cooperation plays a key role in advanced societies with human cooperation among kin being more prominent than cooperation among non-kin. However, little is known about the developmental roots of kin and non-kin cooperation in humans. Here, we show for the first time that children cooperated less successfully with siblings than with non-kin children, whether or not non-kin partners were friends. Furthermore, children with larger social networks cooperated better and the perception of friendship among non-friends improved after cooperating. These results indicate that non-kin cooperation in humans has deep developmental foundations which might serve to forge and extend non-kin social relationships during middle childhood and create opportunities for future collaboration beyond kin. Our results provide a new framework for future studies focusing on how and why cooperation with different classes of partners may change during development in humans as well as other long-lived organisms.
RiceLncPedia: a comprehensive database of rice long non-coding RNAs
Authors: Zhang Zhengfeng , Xu Yao , Yang Fei , Xiao Benze , Li Guoliang
Published: May 2020

Long non-coding RNAs (lncRNAs) play significant functions in various biological processes including differentiation, development and adaptation to different environments. Although multi research focused on lncRNAs in rice, the systematic identification and annotation of lncRNAs expressed in different tissues, developmental stages under diverse conditions are still scarce. This impacts the elucidation of their functional significance and the further research on them. Here, RiceLncPedia (http://218.199.68.191:10092/) is constructed including rice lncRNAs explored from 2313 publically available rice RNA-seq libraries and characterize them with multi-omics data sets. In the current version, RiceLncPedia shows 6978 lncRNAs with abundant features: (i) expression profile across 2313 rice RNA-seq libraries; (ii) an online genome browser for rice lncRNAs; (iii) genome SNPs in lncRNA transcripts; (iv) lncRNA associations with phenotype; (v) overlap of lncRNAs with transposons; and (vi) LncRNA-miRNA interactions and lncRNAs as the precursors of miRNAs. In total, RiceLncPedia imported numerous of rice lncRNAs during development under various environments as well as their features extracted from multi-omics data and thus serve as a fruitful resource for rice-related research communities. RiceLncPedia will be further updated with experimental validation, functions association and epigenetic characteristics to greatly facilitate future investigation on rice lncRNAs.
Using GC content to compare recombination patterns on the sex chromosomes and autosomes of the guppy,Poecilia reticulata, and its close outgroup species
Authors: Charlesworth Deborah , Zhang Yexin , Bergero Roberta , Graham Chay , Gardner Jim , Yong Lengxob
Published: May 2020

Summary/Abstract

Genetic and physical mapping of the guppy (P. reticulata) have shown that recombination patterns differ greatly between males and females. Crossover events occur evenly across the chromosomes in females, but in male meiosis they are restricted to the tip furthest from the centromere of each chromosome, creating very high recombination rates per megabase, similar to the high rates in mammalian sex chromosomes’ pseudo-autosomal regions (PARs). We here used the intronic GC content to indirectly infer the recombination patterns on guppy chromosomes. This is based on evidence that recombination is associated with GC-biased gene conversion, so that genome regions with high recombination rates should be detectable by high GC content. Using intron sequences, which are likely to be under weak selection, we show that almost all guppy chromosomes, including the sex chromosome (LG12) have very high GC values near their assembly ends, suggesting high recombination rates due to strong crossover localisation in male meiosis. Our test does not suggest that the guppy XY pair has stronger crossover localisation than the autosomes, or than the homologous chromosome in a closely related fish, the platyfish (Xiphophorus maculatus). We therefore conclude that the guppy XY pair has not recently undergone an evolutionary change to a different recombination pattern, or reduced its crossover rate, but that the guppy evolved Y-linkage due to acquiring a male-determining factor that also conferred the male crossover pattern. The results also identify the centromere ends of guppy chromosomes, which were not determined in the guppy genome assembly.
Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 infection in the lung epithelium
Authors: Schuler Bryce A. , Habermann A. Christian , Plosa Erin J. , Taylor Chase J. , Jetter Christopher , Kapp Meghan E. , Benjamin John T. , Gulleman Peter , Nichols David S. , Braunstein Lior Z. , Hackett Alice , Koval Michael , Guttentag Susan H. , Blackwell Timothy S. ,   Vanderbilt COVID-19 Consortium Cohort, Webber Steven A. , Banovich Nicholas E. , Kropski Jonathan A. , Sucre Jennifer M. S. ,   HCA Lung Biological Network
Published: May 2020

The SARS-CoV-2 novel coronavirus global pandemic (COVID-19) has led to millions of cases and hundreds of thousands of deaths around the globe. While the elderly appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of the developing mouse lung with temporally-resolved RNA-in-situ hybridization (ISH) in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primerTMPRSS2was highest in ciliated cells and type I alveolar epithelial cells (AT1), andTMPRSS2expression was increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases revealed SARS-CoV-2 RNA was detected most frequently in ciliated and secretory cells in the airway epithelium and AT1 cells in the peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressingTMPRSS2.Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in the lung epithelium, and suggest that developmental regulation ofTMPRSS2may underlie the relative protection of infants and children from severe respiratory illness.
Preprinting the COVID-19 pandemic
Authors: Fraser Nicholas , Brierley Liam , Dey Gautam , Polka Jessica K , Pálfy Máté , Nanni Federico , Coates Jonathon Alexis
Published: May 2020

The world continues to face a life-threatening viral pandemic. The virus underlying the COVID-19 disease, SARS-CoV-2, has caused over 98 million confirmed cases and 2.2 million deaths since January 2020. Although the most recent respiratory viral pandemic swept the globe only a decade ago, the way science operates and responds to current events has experienced a paradigm shift in the interim. The scientific community has responded rapidly to the COVID-19 pandemic, releasing over 125,000 COVID-19 related scientific articles within 10 months of the first confirmed case, of which more than 30,000 were hosted by preprint servers. We focused our analysis on bioRxiv and medRxiv, two growing preprint servers for biomedical research, investigating the attributes of COVID-19 preprints, their access and usage rates, as well as characteristics of their propagation on online platforms. Our data provides evidence for increased scientific and public engagement with preprints related to COVID-19 (COVID-19 preprints are accessed more, cited more, and shared more on various online platforms than non-COVID-19 preprints), as well as changes in the use of preprints by journalists and policymakers. We also find evidence for changes in preprinting and publishing behaviour: COVID-19 preprints are shorter and reviewed faster. Our results highlight the unprecedented role of preprints and preprint servers in the dissemination of COVID-19 science, and the impact of the pandemic on the scientific communication landscape.
The interaction of DNA repair factors ASCC2 and ASCC3 is affected by somatic cancer mutations
Authors: Jia Junqiao , Absmeier Eva , Holton Nicole , Pietrzyk-Brzezinska Agnieszka J. , Hackert Philipp , Bohnsack Katherine E. , Bohnsack Markus T. , Wahl Markus C.
Published: May 2020

The ASCC3 subunit of the activating signal co-integrator complex is a dual-cassette Ski2-like nucleic acid helicase that provides single-stranded DNA for alkylation damage repair by the α-ketoglutarate-dependent dioxygenase, AlkBH3. Other ASCC components integrate ASCC3/AlkBH3 into a complex DNA repair pathway. We mapped and structurally analyzed interacting ASCC2 and ASCC3 regions. The ASCC3 fragment comprises a central helical domain and terminal, extended arms that clasp the compact ASCC2 unit. ASCC2-ASCC3 interfaces are evolutionarily highly conserved and comprise a large number of residues affected by somatic cancer mutations. We quantified contributions of protein regions to the ASCC2-ASCC3 interaction, observing that changes found in cancers lead to reduced ASCC2-ASCC3 affinity. Functional dissection of ASCC3 revealed similar organization and regulation as in the spliceosomal RNA helicase, Brr2. Our results delineate functional regions in an important DNA repair complex and suggest possible molecular disease principles.
A three-dimensional thalamocortical dataset for characterizing brain heterogeneity
Authors: Prasad Judy A. , Balwani Aishwarya H. , Johnson Erik C. , Miano Joseph D. , Sampathkumar Vandana , de Andrade Vincent , Fezzaa Kamel , Du Ming , Vescovi Rafael , Jacobsen Chris , Kording Konrad P. , Gürsoy Doga , Gray-Roncal William , Kasthuri Narayanan , Dyer Eva L.
Published: May 2020

Neural cytoarchitecture is heterogeneous, varying both across and within brain regions. The consistent identification of regions of interest is one of the most critical aspects in examining neurocircuitry, as these structures serve as the vital landmarks with which to map brain pathways. Access to continuous, three-dimensional volumes that span multiple brain areas not only provides richer context for identifying such landmarks, but also enables a deeper probing of the microstructures within. Here, we describe a three-dimensional X-ray microtomography imaging dataset of a well-known and validated thalamocortical sample, encompassing a range of cortical and subcortical structures. In doing so, we provide the field with access to a micron-scale anatomical imaging dataset ideal for studying heterogeneity of neural structure.
Is a Ring-arranged Vascular Pattern Unique to Stems? A Three Dimensional Reconstruction ofAnaxagorea(Annonaceae) Carpel Vasculature and its Evolutionary Implications
Authors: Li Ya , Du Wei , Chen Ye , Wang Shuai , Wang Xiao-Fan
Published: May 2020

Elucidating the origin of carpel has been a challenge in botany for a long time. The Unifying Theory suggested that the carpel originate from a composite organ comprising an ovule-bearing shoot and a foliar part enclosing the shoot. A logical inference from this theory is that placenta in angiosperms should have radiosymmetrical vasculature, just like that in a young branch.Anaxagoreais the most basal genus of the primitive angiosperm family, Annonaceae. The conspicuous carpel stipe makes it an ideal material for exploring the carpel vasculature. In this study, serial sections of flower and carpel were delineated inAnaxagorea luzonensisandA. javanica, and a three-dimensional model of the carpel vasculature was reconstructed. The results show that (1) vascular bundles at both the carpel stipe and the ovule/placenta are in a radiosymmetrical pattern, (2) the amphicribral bundles would develop into ring-arranged bundle complex with the carpel maturation, (3) the ovule/placenta bundles were separated from the bundles of the carpel wall, and, (4) all the radiosymmetrical vasculature (including amphicribral bundles and ring-arranged bundle complexes) in the carpel were fed by a larger radiosymmetrical bundle system. These results suggest that the radiosymmetrical pattern of carpel vasculature are in line with the Unifying Theory.
Study on the expression levels of antibodies against SARS-CoV-2 at different period of disease and its related factors in 192 cases of COVID-19 patients
Authors: Ou Jingyi , Tan Mingkai , He Haolan , Tan Haiyan , Mai Jiewen , Long Yaoxiang , Jiang Xiaowen , He Qing , Huang Ying , Li Yan , Chen Renshen , Li Liya , Li Fang , Shi Yaling
Published: May 2020

Background: In 2020， the current outbreak of Coronavirus Disease 2019(COVID-19) has constituted a global pandemic. But the question about the immune mechanism of patients with COVID-19 is unclear and cause particular concern to the world. Here, we launched a follow-up analysis of antibodies against SARS-CoV-2 of 192 COVID-19 patients, aiming to depict a kinetics profile of antibodies against SARS-CoV-2 and explore the related factors of antibodies expression against SARS-CoV-2 in COVID-19 patient.
Methods: A total of 192 COVID-19 patients enrolled in the designated hospital of Guangzhou , Guangzhou Eighth People's Hospital, from January to February 2020 were selected as the study cohort. A cohort of 130 COVID-19 suspects who had been excluded from SARS-CoV-2 infected by negative RT-PCR result and 209 healthy people were enrolled in this study. Detection of IgM and IgG against SARS-CoV-2 were performed by Chemiluminescence immunoassay in different groups .
Results: It has been found that the seroconversion time of IgM against SARS-CoV-2 in most patients was 5-10 days after the symptoms onset , and then rose rapidly, reaching a peak around 2 to 3 weeks, and the median peak concentration was 2.705 AU / mL. The peak of IgM maintained within one week, and then enters the descending channel. IgG seroconverted later than or synchronously with IgM, reaching peaks around 3 to 4 weeks.The median peak concentration was 33.998AU / ml,which was higher than that of IgM . IgM titers begins to gradually decrease after reaching the peak in the 4th week, after the 8th week, a majority of IgM in patient's serum started to turn negative. On the contrary, titers of IgG began to decline slightly after the fifth week, and more than 90% of results of patients were positive after 8 weeks. Additionally, the concentration of antibodies positively correlated with the severity of the disease and the duration of virus exist in host.
Conclusion: We depict a kinetics profile of antibodies against SARS-CoV-2 in COVID-19 patients and found out that the levels of antibodies were related to the disease severity,age, gender and virus clearance or continuous proliferation of COVID-19 patients.
High-throughput immunoassays for SARS-CoV-2 – considerable differences in performance when comparing three methods
Authors: Ekelund Oskar , Ekblom Kim , Somajo Sofia , Pattison-Granberg Johanna , Olsson Karl , Petersson Annika
Published: May 2020

Background

The recently launched high-throughput assays for the detection of antibodies against SARS-CoV-2 may change the managing strategies for the COVID-19 pandemic. This study aimed at investigating the performance of three high-throughput assays and one rapid lateral flow test relative to the recommended criteria defined by regulatory authorities.

Methods

A total of 133 samples, including 100 pre-pandemic samples, 20 samples from SARS-CoV-2 RT-PCR positive individuals, and 13 potentially cross-reactive samples were analysed with SARS-CoV-2 IgG (Abbott), Elecsys Anti-SARS-CoV-2 (Roche), LIAISON SARS-CoV-2 S1/S2 IgG (DiaSorin) and 2019-nCOV IgG/IgM Rapid Test (Dynamiker Biotechnology Co).

Results

All assays performed with a high level of specificity; however, only Abbott reached 100% (95% CI 96.3-100). The pre-pandemic samples analysed with Roche, DiaSorin and Dynamiker Biotechnology resulted in two to three false-positive results per method (specificity 96.9-98.0%). Sensitivity differed more between the assays, Roche exhibiting the highest sensitivity (100%, CI 83.9-100). The corresponding figures for Abbott, DiaSorin and Dynamiker Biotechnology were 85.0%, 77.8% and 75.0%, respectively.

Conclusions

The results of the evaluated SARS-CoV-2 assays vary considerably as well as their ability to fulfil the performance criteria proposed by regulatory authorities. Introduction into clinical use in low-prevalent settings, should therefore, be made with caution.
Knowledge, attitude, and practices of Community pharmacists about COVID-19: A cross-sectional survey in two provinces of Pakistan
Authors: Muhammad Khayal , Saqlain Muhammad , Hamdard Ataullah , Naveed Muhammad , Umer Muhammad Farooq , Khan Siraj , Kamran Muhammad , Rashid Haroon , Kamran Sohail , Khan Muhammad Ijaz , Khan Faiz Ullah , Hussain Yaseen , Khan Zakir
Published: May 2020

Amidst to current Coronavirus infectious disease 2019 (COVID-19) pandemic, the international pharmaceutical federation stated that pharmacists being a part of the healthcare system had a crucial role in the management cycle of COVID-19 outbreak. The purpose of this study was to assess the knowledge, attitude and practice of community pharmacists, to snapshot their current preparedness and awareness regarding COVID-19. An online survey was conducted among a sample of 393 community pharmacists from two provinces; Punjab and Khyber-Pakhtunkhwa, Pakistan during a period of strict lockdown (10th to 30th April 2020). A validated (Cronbach alpha= 0.077) self-administered questionnaire comprised of five sections (Demographics, source of information, knowledge, attitude, and practice) was used for data collection. Logistic regression was applied to find potential factors associated with good knowledge, attitude, and practice by using SPSS version 21. Of total 393 participants, 71.5% (n=281) had good knowledge, 44% (n=175) had positive attitude and 57.3% (n=225) had good practice regarding COVID-19. Social media (45.29%, n=178) was reported as the main source to seek information regarding COVID-19. Results revealed that the age of ≥26 years, Ph.D. degree level, and good knowledge were the substantial determinants (P<0.05) of a good attitude. Similarly, community pharmacist who had an experience of >5 years, hold a Ph.D. degree, good knowledge and good attitude had higher odds of good practice compared to reference categories (P<0.05). The findings demonstrated that the majority of community pharmacists had good knowledge, but had a poor attitude and practice towards the COVID-19. This study also highlighted the disparity in some aspects of knowledge, attitude, and practice that must be addressed in future educational, awareness, and counselling programs.
A Noncooperative Game Analysis for Controlling COVID-19 Outbreak
Authors: Bairagi Anupam Kumar , Masud Mehedi , Kim Do Hyeon , Munir Md. Shirajum , Al Nahid Abdullah , Abedin Sarder Fakhrul , Alam Kazi Masudul , Biswas Sujit , Alshamrani Sultan S , Han Zhu , Hong Choong Seon
Published: May 2020

COVID-19is a global epidemic. Till now, there is no remedy for this epidemic. However, isolation and social distancing are seemed to be effective to control this pandemic. In this paper, we provide an analytical model on the effectiveness of the sustainable lockdown policy that accommodates both isolation and social distancing features of the individuals. To promote social distancing, we analyze a noncooperative game environment that provides an incentive for maintaining social distancing. Furthermore, the sustainability of the lockdown policy is also interpreted with the help of a game-theoretic incentive model for maintaining social distancing. Finally, an extensive numerical analysis is provided to study the impact of maintaining a social-distancing measure to prevent the Covid-19 outbreak. Numerical results show that the individual incentive increases more than 85% with an increasing percentage of home isolation from 25% to 100% for all considered scenarios. The numerical results also demonstrate that in a particular percentage of home isolation, the individual incentive decreases with an increasing number of individuals.
Lung epithelial stem cells express SARS-CoV-2 entry factors: implications for COVID-19
Authors: Valyaeva Anna A. , Zharikova Anastasia A. , Kasianov Artem S. , Vassetzky Yegor S. , Sheval Eugene V.
Published: May 2020

SARS-CoV-2 can infiltrate the lower respiratory tract, resulting in severe respiratory failure and a high death rate. Normally, the airway and alveolar epithelium can be rapidly reconstituted by multipotent stem cells after episodes of infection. Here, we analyzed published RNA-seq datasets and demonstrated that cells of four different lung epithelial stem cell types express SARS-CoV-2 entry factors, includingAce2. Thus, stem cells can be potentially infected by SARS-CoV-2, which may lead to defects in regeneration capacity partially accounting for the severity of SARS-CoV-2 infection and its consequences.
Visualizing orientation-specific relaxation-diffusion features mapped onto orientation distribution functions estimated via nonparametric Monte Carlo MRI signal inversion
Authors: de Almeida Martins João P. , Tax Chantal M. W. , Reymbaut Alexis , Szczepankiewicz Filip , Jones Derek K. , Topgaard Daniel
Published: May 2020

Diffusion MRI techniques are widely used to studyin vivochanges in the human brain connectome. However, to resolve and characterise white matter fibres in heterogeneous diffusion MRI voxels remains a challenging problem typically approached with signal models that rely on prior information and restrictive constraints. We have recently introduced a 5D relaxation-diffusion correlation framework wherein multidimensional diffusion encoding strategies are used to acquire data at multiple echo-times in order to increase the amount of information encoded into the signal and ease the constraints needed for signal inversion. Nonparametric Monte Carlo inversion of the resulting datasets yields 5D relaxation-diffusion distributions where contributions from different sub-voxel tissue environments are separated with minimal assumptions on their microscopic properties. Here, we build on the 5D correlation approach to derive fibre-specific metrics that can be mapped throughout the imaged brain volume. Distribution components ascribed to fibrous tissues are resolved, and subsequently mapped to a dense mesh of overlapping orientation bins in order to define a smooth orientation distribution function (ODF). Moreover, relaxation and diffusion measures are correlated to each independent ODF coordinate, thereby allowing the estimation of orientation-specific relaxation rates and diffusivities. The proposed method is tested on a healthy volunteer, where the estimated ODFs were observed to capture major WM tracts, resolve fibre crossings, and, more importantly, inform on the relaxation and diffusion features along distinct fibre bundles. If combined with fibre-tracking algorithms, the methodology presented in this work may be useful for investigating the microstructural properties along individual white matter pathways.
Bepridil is potent against SARS-CoV-2 In Vitro
Authors: Vatansever Erol C. , Yang Kai , Kratch Kaci C. , Drelich Aleksandra , Cho Chia-Chuan , Mellott Drake M. , Xu Shiqing , Tseng Chien-Te K. , Liu Wenshe Ray
Published: May 2020

Guided by a computational docking analysis, about 30 FDA/EMA-approved small molecule medicines were characterized on their inhibition of the SARS-CoV-2 main protease (MPro). Of these tested small molecule medicines, six displayed an IC50value in inhibiting MProbelow 100 μM. Three medicines pimozide, ebastine, and bepridil are basic small molecules. Their uses in COVID-19 patients potentiate dual functions by both raising endosomal pH to slow SARS-CoV-2 entry into the human cell host and inhibiting MProin infected cells. A live virus-based microneutralization assay showed that bepridil inhibited cytopathogenic effect induced by SARS-CoV-2 in Vero E6 cells completely at and dose-dependently below 5 μM and in A549 cells completely at and dose-dependently below 6.25 μM. Therefore, the current study urges serious considerations of using bepridil in COVID-19 clinical tests.
Evidence for prescribed NK cell Ly49 developmental pathways in mice
Authors: Millan Alberto J. , Hom Bryan A. , Libang Jeremy B. , Sindi Suzanne , Manilay Jennifer O.
Published: May 2020

Previous studies of NK cell inhibitory Ly49 receptors suggested their expression is stochastic. However, relatively few studies have examined this stochasticity in conjunction with activating Ly49 receptors. We hypothesized that the expression of activating Ly49 receptors is not stochastic and is influenced by inhibitory Ly49 receptors. We analyzed NK cell “clusters” defined by combinatorial expression of activating (Ly49H, Ly49D) and inhibitory (Ly49I, Ly49G2) receptors in C57BL/6 mice. Using the product rule to evaluate the interdependencies of the Ly49 receptors, we found evidence for a tightly regulated expression at the immature NK cell stage, with the highest interdependencies between clusters that express at least one activating receptor. Further analysis demonstrated that certain NK clusters predominated at the immature (CD27+CD11b−), transitional (CD27+CD11b+) and mature (CD27−CD11b−) NK cell stages. Using parallel in vitro culture and in vivo transplantation of sorted NK clusters, we discovered non-random upregulation of Ly49 receptors, suggesting that prescribed pathways of NK cluster differentiation exist. Our data infer that upregulation of Ly49I is an important step in NK cell maturation. Ki-67 expression and cell counts confirmed that immature NK cells proliferate more than mature NK cells. We found that MHC-I is particularly important for regulation of Ly49D and Ly49G2, even though no known MHC-I ligand for these receptors is present in B6 mice. Our data indicate that the regulatory systems controlling the expression of both activating and inhibitory Ly49 receptors are non-stochastic and support the idea that NK cell clusters develop in a non-random process correlated to their maturation stage.
The stringent stress response controls proteases and global regulators under optimal growth conditions inPseudomonas aeruginosa
Authors: Pletzer Daniel , Blimkie Travis M. , Wolfmeier Heidi , Li Yicong , Baghela Arjun , Lee Amy H. Y. , Falsafi Reza , Hancock Robert E. W.
Published: May 2020

The bacterial stringent stress response, mediated by the signaling molecule guanosine tetra-phosphate, ppGpp, has recently gained attention as being important during normal cellular growth and as potential new therapeutic target, which warrants detailed mechanistic understanding. Here, we used intracellular protein tracking inPseudomonas aeruginosaPAO1, which indicated that RelA was bound to the ribosome, while SpoT localized at the cell poles. RNA-Seq was used to investigate the transcriptome of a ppGpp-deficient strain under non-stressful nutrient-rich broth conditions where the mutant grew at the same rate as the parent strain. In exponential growth phase, the lack of ppGpp led to >1,600 transcriptional changes (fold-change cut-off ±1.5), providing further novel insights into the normal physiological role of ppGpp. The stringent response was linked to gene expression of various proteases and secretion systems includingaprA, PA0277,impA, andclpP2. The previously observed reduction in cytotoxicity towards red blood cells, in a stringent response mutant, appeared to be due toaprA. Investigation of anaprAmutant in a murine skin infection model, showed increased survival rates of theaprAmutant consistent with previous observations that stringent-response mutants have reduced virulence. In addition, the overexpression ofrelA, but not induction of ppGpp with serine hydroxamate, dysregulated global transcriptional regulators as well as >30% of the regulatory networks controlled by AlgR, OxyR, LasR, and AmrZ. Together these data expand our knowledge about ppGpp and its regulatory network and role in environmental adaptation. It also confirms its important role throughout the normal growth cycle of bacteria.

Significance Statement

Microorganisms need to adapt rapidly to survive harsh environmental changes. Here, we showed the broad influence of the highly studied bacterial stringent stress response under non-stressful conditions that indicate its general physiological importance and might reflect the readiness of bacteria to respond to and activate acute stress responses. Using RNA-Seq to investigate the transcriptional network ofPseudomonas aeruginosacells revealed that >30% of all genes changed expression in a stringent-response mutant under optimal growth conditions. This included genes regulated by global transcriptional regulators and novel downstream effectors. Our results help to understand the importance of this stress regulator in bacterial lifestyle under relatively unstressed conditions. As such it draws attention to the consequences of targeting this ubiquitous bacterial signaling molecule.
Suspected COVID-19 in primary care: how GP records contribute to understanding differences in prevalence by ethnicity.
Authors: Hull Sally A , Williams Crystal , Ashworth Mark , Carvalho Chris , Boomla Kambiz
Published: May 2020

Abstract
Background
The first wave of the London COVID-19 epidemic peaked in April 2020. Attention initially focussed on severe presentations, intensive care capacity, and the timely supply of equipment. General practice has seen a rapid take up of technology to allow virtual consultations, enabling the management of mild and moderate community cases.

Aim
To quantify the prevalence and time-course of suspected COVID-19 presenting to general practices during the London epidemic. To report disease prevalence by ethnic group, and explore how far differences by ethnicity can be explained by data in the electronic health record (EHR).

Design and Setting
Cross-sectional study using anonymised data from the primary care records of 1.3 million people registered with 157 practices in four adjacent east London clinical commissioning groups (CCGs). The study area includes 48% of people from ethnic minorities and is in the top decile of social deprivation in England.

Method
Suspected COVID-19 cases were identified using SNOMED codes.
Explanatory variables included age, gender, self-reported ethnicity and measures of social deprivation. Clinical factors included 16 long-term conditions, latest body mass index and smoking status.

Results
There were 8,985 suspected COVID-19 cases. Ethnicity recording was 78% complete.
Univariate analysis showed a two-fold increase in odds of infection for South Asian and Black adults compared to White. In a fully adjusted analysis, including clinical factors, the odds were: South Asian OR 1.93 (95% CI = 1.83 to 2.04) Black OR 1.47 (95% CI 1.38 to 1.57)

Conclusions
Using data in GP records Black and south Asian ethnicity remain as predictors of community cases of COVID-19, with levels of risk similar to hospital admission cases. Further understanding of these differences requires social and occupational data.
COVID-19 impact on consecutive neurological patients admitted to the emergency department
Authors: Pilotto Andrea , Benussi Alberto , Libri Ilenia , Masciocchi Stefano , Poli Loris , Premi Enrico , Alberici Antonella , Baldelli Enrico , Bonacina Sonia , Brambilla Laura , Benini Matteo , Caratozzolo Salvatore , Cortinovis Matteo , Costa Angelo , Piccinelli Stefano Cotti , Cottini Elisabetta , Cristillo Viviana , Delrio Ilenia , Filosto Massimiliano , Gamba Massimo , Gazzina Stefano , Gilberti Nicola , Gipponi Stefano , Giunta Marcello , Imarisio Alberto , Liberini Paolo , Locatelli Martina , Cola Francesca Schiano di , Rao Renata , Risi Barbara , Rozzini Luca , Scalvini Andrea , Vergani Veronica , Volonghi Irene , Zoppi Nicola , Borroni Barbara , Magoni Mauro , Leonardi Matilde , Zanusso Gianluigi , Ferrari Sergio , Mariotto Sara , Pezzini Alessandro , Gasparotti Roberto , Paolillo Ciro , Padovani Alessandro
Published: May 2020

Objective

Aim of this study was to analyse the impact of COVID-19 on clinical and laboratory findings and outcome of neurological patients consecutively admitted to the emergency department (ED) of a tertiary hub center.

Methods

All adult patients consecutively admitted to the ED for neurological manifestations from February 20th through April 30th 2020 at Spedali Civili of Brescia entered the study. Demographic, clinical, and laboratory data were extracted from medical records and compared between patients with and without COVID-19.

Results

Out of 505 consecutively patients evaluated at ED with neurological symptoms, 147 (29.1%) tested positive for SARS-CoV-2. These patients displayed at triage higher values of CRP, AST, ALT, and fibrinogen but not lymphopenia (p<0.05). They were older (73.1 ± 12.4 vs 65.1 ± 18.9 years, p=0.001) had higher frequency of stroke (34.7% vs 29.3%), encephalitis/meningitis (9.5% vs 1.9%) and delirium (16.3% vs 5.0%). Compared to patients without COVID, they were more frequently hospitalized (91.2% vs 69.3%, p<0.0001) and showed higher mortality rates (29.7% vs 1.8%, p<0.0.001) and discharge disability, independently from age.

Conclusions

COVID-19 impacts on clinical presentation of neurological disorders, with higher frequency of stroke, encephalitis and delirium, and was strongly associated with increased hospitalisation, mortality and disability.
A Consensus Transcriptional Landscape of Human End-Stage Heart Failure
Authors: Flores Ricardo O. Ramirez , Lanzer Jan D. , Holland Christian H. , Leuschner Florian , Most Patrick , Schultz Jobst-Hendrik , Levinson Rebecca T. , Saez-Rodriguez Julio
Published: May 2020

2.

Aims

Transcriptomic studies have contributed to fundamental knowledge of myocardial remodeling in human heart failure (HF). However, the agreement on key regulated genes in HF is limited and systematic efforts to integrate evidence from multiple patient cohorts are lacking. Here we aimed to provide an unbiased consensus transcriptional signature of human end-stage HF by comprehensive comparison and analysis of publicly available datasets.

Methods and Results

We curated and uniformly processed 16 public transcriptomic studies of left ventricular samples from 263 healthy and 653 failing human hearts. Transfer learning approaches revealed conserved disease patterns across all studies independent of technical differences. We meta-analyzed the dysregulation of 14041 genes to extract a consensus signature of HF. Estimation of the activities of 343 transcription factors, 14 signalling pathways, and 182 micro RNAs, as well as the enrichment of 5998 biological processes confirmed the established aspects of the functional landscape of the disease and revealed novel ones. We provide all results in a free public resource https://saezlab.shinyapps.io/reheat/ to facilitate further use and interpretation of the results. We exemplify usage by deciphering fetal gene reprogramming and tracing myocardial origin of the plasma proteome biomarkers in HF patients.

Conclusion

We demonstrated the feasibility of combining transcriptional studies from different HF patient cohorts. This compendium provides a robust and consistent collection of molecular markers of end-stage HF that may guide the identification of novel targets with diagnostic or therapeutic relevance.
Incubation period of COVID-19 in the “live-house” cluster of accurately known infection events and delay time from symptom onset of public reporting observed in cases in Osaka, Japan
Authors: Tomie Toshihisa
Published: May 2020

The incubation period of an infectious disease is very important for control of the disease but estimating the period is not easy because the date of infection is not easy to identify. Accurate incubation period distribution by examining cases in the cluster generated in “live-houses” in Osaka, Japan with known infection events is reported. The distribution of the latent period is also estimated. The modes of incubation and latent periods of COVID-19 in Japan are 4.1 days and 3.3 days, respectively. The mode of the delay time from the onset to reporting is estimated to be 4.7 days, telling that the effects of interventions show up in the number of infections two weeks later after the measures.