bluuebunny/crossref_metadata_2025 huggingface dataset:
SeSaMe PS Function: Functional Analysis of the Whole Metagenome Sequencing Data of the Arbuscular Mycorrhizal Fungi
Authors: Kang Jee Eun , Ciampi Antonio , Hijri Mohamed
Published: May 2020

In this article, we introduce a novel bioinformatics program- SeSaMe PS Function (Spore associated Symbiotic Microbes Position Specific Function) - for position-specific functional analysis of short sequences derived from metagenome sequencing data of the arbuscular mycorrhizal fungi. The unique advantage of the program lies in databases created based on genus-specific sequence properties derived from protein secondary structure, namely amino acid usages, codon usages, and codon contexts of three codon DNA 9-mers. SeSaMe PS Function searches a query sequence against reference sequence database, identifies three codon DNA 9-mers with structural roles, and dynamically creates the comparative dataset of 54 microbial genera based on their codon usage biases. The program applies correlation Principal Component Analysis in conjunction with K-means clustering method to the comparative dataset. Three codon DNA 9-mers clustered as sole member or with only a few members are often structurally and functionally distinctive sites that provide useful insights into important molecular interactions. The program provides a versatile means for studying functions of short sequences from metagenome sequencing and has a wide spectrum of applications.
Modeling and Forecasting of Covid-19 growth curve in India
Authors: Sharma Vikas Kumar , Nigam Unnati
Published: May 2020

In this article, we analyze the growth pattern of Covid-19 pandemic in India from March 4th to July 11th using regression analysis (exponential and polynomial), auto-regressive integrated moving averages (ARIMA) model as well as exponential smoothing and Holt-Winters smoothing models. We found that the growth of Covid-19 cases follows a power regime of (t2,t,..) after the exponential growth. We found the optimal change points from where the Covid-19 cases shift their course of growth from exponential to quadratic and then from quadratic to linear. After that, we saw a sudden spike in the course of the spread of Covid-19 and the growth moved from linear to quadratic and then to quartic, which is alarming. We have also found the best fitted regression models using the various criteria such as significant p-values, coefficients of determination and ANOVA etc. Further, we search the best fitting ARIMA model for the data using the AIC (Akaike Information Criterion) and provide the forecast of Covid-19 cases for future days. It was noticed that the ARIMA model fits better the Covid-19 cases for small regions. ARIMA (5, 2, 5) and ARIMA (5, 2, 3) are the best possible models for modeling Covid-19 cases for March 4th to July 10th and June 1th to July 10th, respectively.
Modelling information–dependent social behaviors in response to lockdowns: the case of COVID–19 epidemic in Italy
Authors: Buonomo Bruno , Marca Rossella Della
Published: May 2020

The COVID–19 pandemic started in January 2020 has not only threatened world public health, but severely impacted almost every facet of lives including behavioral and psychological aspects. In this paper we focus on the ‘human element’ and propose a mathematical model to investigate the effects on the COVID–19 epidemic of social behavioral changes in response to lockdowns. We consider a SEIR-like epidemic model where that contact and quarantine rates are assumed to depend on the available information and rumors about the disease status in the community. The model is applied to the case of COVID–19 epidemic in Italy. We consider the period that stretches between Bebruary 24, 2020 when the first bulletin by the Italian Civil Brotection was reported and May 18, 2020 when the lockdown restrictions have been mostly removed. The role played by the information–related parameters is determined by evaluating how they affect suitable outbreak–severity indicators. We estimated that citizens compliance with mitigation measures played a decisive role in curbing the epidemic curve by preventing a duplication of deaths and about 46% more contagions.

Subject class:92D30, 34C60
Management of mild COVID-19: Policy implications of initial experience in India
Authors: Kumar Rohit , Bhattacharya Bisakh , Meena Ved Prakash , Aggarwal Anivita , Tripathi Manasi , Soneja Manish , Mittal Ankit , Singh Komal , Gupta Nishkarsh , Garg Rakesh Kumar , Ratre Brajesh Kumar , Kumar Balbir , Bhopale Shweta Arun , Tiwari Pavan , Verma Ankit , Bhatnagar Sushma , Mohan Anant , Wig Naveet , Guleria Randeep
Published: May 2020

Objectives

Ongoing pandemic due to COVID-19 has spread across countries, surprisingly with variable clinical characteristics and outcomes. This study was aimed at describing clinical characteristics and outcomes of admitted patients with mild COVID-19 illness in the initial phase of pandemic in India.

Design

Retrospective (observational) study.

Setting

COVID facilities under AIIMS, New Delhi, where, isolation facilities were designed to manage patients with mild illness and dedicated COVID ICUs was created to cater patients with moderate to severe illness.

Participants

Patients aged 18 years or more, with confirmed illness were eligible for enrolment. Patients who were either asymptomatic or mildly ill at presentation were included. Patients with moderate to severe illness at admission, or incomplete clinical symptomatology records were excluded.

Methods

Data regarding demographic profile, comorbidities, clinical features, hospital course, treatment, details of results of RT-PCR for SARS-CoV-2 done at baseline and at day 14, chest radiographs (wherever available) as well as laboratory parameters was obtained retrospectively from the hospital records.

Main outcome measures

Final outcome was noted in terms of course of the disease, patients discharged, still admitted (at time of conclusion of study) or death.

Results

Out of 231 cases included, majority were males(78·3%) with a mean age of 39·8 years. Comorbidities were present in 21·2% of patients, diabetes mellitus and hypertension being most common. The most common symptoms were dry cough(81, 35%), fever(64, 27·7%), sore throat(36, 15·6%), and dyspnoea(24, 10·4%); asymptomatic infection was noted in 108(46.8%) patients. Presence of comorbidities was an independent predictor of symptomatic disease (OR- 2·66; 95% CI 1·08 to 6·53, p= 0·03). None of the patients progressed to moderate to severe COVID-19. There were no deaths in this cohort.

Conclusions

Patients with mild disease at presentation had a stable disease course and therefore such cases can be managed outside hospital setting. A large proportion of patients remained asymptomatic throughout the course of infection and those with comorbidities are more likely to be symptomatic.

Trial registration

Not applicable
Decentralized governance may lead to higher infection levels and sub-optimal releases of quarantines amid the COVID-19 pandemic
Authors: Lampert Adam
Published: May 2020

The outbreak of the novel Coronavirus (COVID-19) has led countries worldwide to administer quarantine policies. However, each country or state decides independently what mobility restrictions to administer within its borders, while aiming to maximize its own citizens’ welfare. Since individuals travel between countries and states, the policy in one country affects the infection levels in other countries. Therefore, major question is whether the policies dictated by multiple governments could be efficient. Here we focus on the decision regarding the timing of releasing quarantines, which were common during the first year of the pandemic. We consider a game-theoretical epidemiological model in which each government decides when to switch from a restrictive to a non-restrictive quarantine and vice versa. We show that, if travel between countries is frequent, then the policy dictated by multiple governments is sub-optimal. But if international travel is restricted, then the policy may become optimal.
Comparison of induced neurons reveals slower structural and functional maturation in humans than in apes
Authors: Schörnig Maria , Ju Xiangchun , Fast Luise , Weigert Anne , Schaffer Theresa , Ebert Sebastian , Treutlein Barbara , Kasri Nael Nadif , Peter Benjamin , Hevers Wulf , Taverna Elena
Published: May 2020

We generated induced excitatory sensory neurons (iNeurons, iNs) from chimpanzee, bonobo and human stem cells by expressing the transcription factor neurogenin-2 (NGN2). Single cell-RNA sequencing showed that genes involved in dendrite and synapse development are expressed earlier during iNs maturation in the chimpanzee than the human cells. In accordance, during the first two weeks of differentiation, chimpanzee and bonobo iNs showed repetitive action potentials and more spontaneous excitatory activity than human iNs, and extended neurites of higher total length. However, the axons of human iNs were slightly longer at 5 weeks of differentiation. The timing of the establishment of neuronal polarity did not differ between the species. Chimpanzee, bonobo and human neurites eventually reached the same level of structural complexity. Thus, human iNs develop slower than chimpanzee and bonobo iNs and this difference in timing likely depends on functions downstream of NGN2.
Controlling the switch from neurogenesis to pluripotency during marmoset monkey somatic cell reprogramming with self-replicating mRNAs and small molecules
Authors: Petkov Stoyan , Dressel Ralf , Rodriguez-Polo Ignacio , Behr Rüdiger
Published: May 2020

Induced pluripotent stem cells (iPSCs) hold enormous potential for the development of cell-based therapies for many currently incurable diseases. However, the safety and efficacy of potential iPSC-based treatments need to be verified in relevant animal disease models before their application in the clinic. Moreover, in order to reduce possible risks for the patients, it is necessary to use reprogramming approaches that ensure to the greatest extent possible the genomic integrity of the cells. Here, we report the derivation of iPSCs from common marmoset monkeys (Callithrix jacchus) using self-replicating mRNA vectors based on the Venezuelan equine encephalitis virus (VEE-mRNAs). By transfection of marmoset fetal fibroblasts with Tomato-modified VEE-mRNAs carrying the humanOCT4, KLF4, SOX2, andc-MYC(VEE-OKS-iM-iTomato) and culture in medium supplemented with two small molecule inhibitors, we first established intermediate primary colonies with neural progenitor-like properties. In the second reprogramming step, we converted these colonies into transgene-free pluripotent stem cells by further culturing them with customized marmoset iPSC medium in feeder-free conditions. The resulting cell lines possess pluripotency characteristics, such as expression of various pluripotency markers, long-term self-renewal, stable karyotype, and ability to differentiate into derivatives of the three primary germ layersin vitroandin vivo. Our experiments reveal a novel paradigm for flexible reprogramming of somatic cells, where primary colonies obtained by a single VEE-mRNA transfection can be directed either towards the neural lineage or further reprogrammed to pluripotency. These results (i) will further enhance the role of the common marmoset as animal disease model for preclinical testing of iPSC-based therapies and (ii) establish an in vitro system to experimentally address developmental signal transduction pathways in primates.
Development of Microsatellite Markers for a Soricid Water ShrewChimarrogale platycephalus, and the Success of Individual Identification Using It
Authors: Yamazaki Haruka , Sekiya Tomohiro , Nagayama Shun , Hirasawa Kei , Tokura Keita , Sasaki Akio , Ichiyanagi Hidetaka , Tojo Koji
Published: May 2020

The soricid water shrew,Chimarrogale platycephalus, is a mammal species endemic to the Japanese Islands. They inhabit the islands of Honshu and Kyushu, and are considered to be extinct in Shikoku. Information on this water shrew from Honshu and Kyushu is also scarce, andC. platycephalusis registered on the Japanese Government’s red list as an endangered species. Almost all study areas such as regarding their ethology, ecology, also their phylogenetics are lacking. The delay in these foundational studies is due to difficulties related to them being both nocturnal and aquatic. In order to study ofC. platycephalus, it is essential to conduct field research in mountain streams at night under such circumstances. In response to such difficult circumstances, we established a genetic analysis method using the feces ofC. platycephalus, and as a result the accumulation of data on their phylogenetic evolution and phylogeography has increased which has improved our understanding of this species. Furthermore in this study, development of microsatellite markers was carried out, and a total of 21 loci marker analyses were performed. In addition, in order to confirm the credibility of these 21 microsatellite markers, as being able to validly differentiate individuals, all markers were examined using the fecal and tissues specimens from verified separately reared individuals (12 individuals) with the known history of having been reared in an aquarium. As a result, it was revealed that if analyses of the 12 loci were possible, individual differentiation with 100% accuracy was possible. The development of microsatellite markers in this study, and the establishment of individual identification methods by means of this will be expected to greatly contribute to future ecological and ethological research, population genetics and biogeographical research of the water shrew,C. platycephalus.
Treatment with valproate downregulates theAgtr2mRNA in rat lungs
Authors: Seppa Kadri , Terasmaa Anton , Jagomäe Toomas , Innos Jürgen , Vasar Eero , Plaas Mario
Published: May 2020

GLP1 receptor agonist liraglutide has been shown to upregulate ACE2 expressions in several animal studies and thereby mediate strong positive stress response1. On the other hand, two in silico studies suggest that valproate downregulates ACE2 and AGTR2 gene expressions2,3. In this study, we have evaluated how these two widely used drugs, liraglutide and valproate, change the expression pattern of RAS system genes in the rat lungs. Our results indicate that eight-day treatment with valproate significantly downregulates the gene expression ofAgtr2, Mas1andAgrt1bin the rat lungs. These effects are reversed by co-administration of liraglutide.
A workflow for accurate metabarcoding using nanopore MinION sequencing
Authors: Baloğlu Bilgenur , Chen Zhewei , Elbrecht Vasco , Braukmann Thomas , MacDonald Shanna , Steinke Dirk
Published: May 2020

Metabarcoding has become a common approach to the rapid identification of the species composition in a mixed sample. The majority of studies use established short-read high-throughput sequencing platforms. The Oxford Nanopore MinION™, a portable sequencing platform, represents a low-cost alternative allowing researchers to generate sequence data in the field. However, a major drawback is the high raw read error rate that can range from 10% to 22%.

To test if the MinION™ represents a viable alternative to other sequencing platforms we used rolling circle amplification (RCA) to generate full-length consensus DNA barcodes (658bp of cytochrome oxidase I - COI) for a bulk mock sample of 50 aquatic invertebrate species. By applying two different laboratory protocols, we generated two MinION™ runs that were used to build consensus sequences. We also developed a novel Python pipeline, ASHURE, for processing, consensus building, clustering, and taxonomic assignment of the resulting reads.

We were able to show that it is possible to reduce error rates to a median accuracy of up to 99.3% for long RCA fragments (>45 barcodes). Our pipeline successfully identified all 50 species in the mock community and exhibited comparable sensitivity and accuracy to MiSeq. The use of RCA was integral for increasing consensus accuracy, but it was also the most time-consuming step during the laboratory workflow and most RCA reads were skewed towards a shorter read length range with a median RCA fragment length of up to 1262bp. Our study demonstrates that Nanopore sequencing can be used for metabarcoding but we recommend the exploration of other isothermal amplification procedures to improve consensus length.
Multilayer modelling and analysis of the human transcriptome
Authors: Azevedo Tiago , Dimitri Giovanna Maria , Lio Pietro , Gamazon Eric R.
Published: May 2020

Here, we performed a comprehensive intra-tissue and inter-tissue network analysis of the human transcriptome. We generated an atlas of communities in co-expression networks in 49 tissues (GTEx v8), evaluated their tissue specificity, and investigated their methodological implications. UMAP embeddings of gene expression from the communities (representing nearly 18% of all genes) robustly identified biologically-meaningful clusters. Methodologically, integration of the communities into a transcriptome-wide association study of C-reactive protein (CRP) in 361,194 individuals in the UK Biobank identified genetically-determined expression changes associated with CRP and led to considerably improved performance. Furthermore, a deep learning framework applied to the communities in nearly 11,000 tumours profiled by The Cancer Genome Atlas across 33 different cancer types learned biologically-meaningful latent spaces, representing metastasis (p< 2.2 × 10−16) and stemness (p< 2.2 × 10−16). Our study provides a rich genomic resource to catalyse research into inter-tissue regulatory mechanisms and their downstream phenotypic consequences.
Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis, and Poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets
Authors: Mavian Carla , Ramirez-Mata Andrea S. , Dollar James Jarad , Nolan David J. , White Kevin , Rich Shannan N. , Magalis Brittany Rife , Cash Melanie , Marini Simone , Prosperi Mattia C. F. , Amador David Moraga , Riva Alberto , Williams Kenneth C. , Salemi Marco
Published: May 2020

Background

Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals’ quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been identified.

Results

We investigated transcriptomic profiles in frontal cortex tissues of Simian immunodeficiency virus (SIV)-infected Rhesus macaques sacrificed at different stages of infection. Gene expression was compared among SIV-infected animals (n=11), with or without CD8+ lymphocyte depletion, based on detectable (n=6) or non-detectable (n=5) presence of the virus in frontal cortex tissues. Significant enrichment in activation of monocyte and macrophage cellular pathways was found in animals with detectable brain infection, independently from CD8+ lymphocyte depletion. In addition, transcripts of four poly (ADP-ribose) polymerases (PARPs) were up-regulated in the frontal cortex, which was confirmed by real-time polymerase chain reaction.

Conclusions

Our results shed light on involvement of PARPs in SIV infection of the brain and their role in SIV-associated neurodegenerative processes. Inhibition of PARPs may provide an effective novel therapeutic target for HIV-related neuropathology.
Development of novel apoptosis-assisted lung tissue decellularization methods
Authors: Song Young Hye , Maynes Mark A , Hlavac Nora , Visosevic Daniel , Daramola Kaitlyn O , Porvasnik Stacy L , Schmidt Christine E
Published: May 2020

Decellularized tissues hold great potential for both regenerative medicine and disease modeling applications. The acellular extracellular matrix (ECM)-enriched scaffolds can be recellularized with patient-derived cells prior to transplantation, or digested to create thermally-gelling hydrogels for 3D cell culture. Current methods of decellularization clear cellular components using detergents, which can result in loss of ECM proteins and tissue architectural integrity. Recently, an alternative approach utilizing apoptosis to decellularize excised murine sciatic nerves resulted in superior ECM preservation, cell removal, and immune tolerancein vivo. However, this apoptosis-assisted decellularization approach has not been optimized for other tissues with a more complex geometry, such as lungs. To this end, we developed an apoptosis-assisted lung tissue decellularization method using a combination of camptothecin and sulfobetaine-10 (SB-10) to induce apoptosis and facilitate gentle and effective removal of cell debris, respectively. Importantly, combination of the two agents resulted in superior cell removal and ECM preservation compared to either of the treatments alone, presumably because of pulmonary surfactants. In addition, our method was superior in cell removal compared to a previously established detergent-based decellularization protocol. Furthermore, thermally-gelling lung ECM proteins supported high viability of rat lung epithelial cells for up to 2 weeks in culture. This work demonstrates that apoptosis-based lung tissue decellularization is a superior technique that warrants further utilization for both regenerative medicine and disease modeling applications.
Natural Genetic Variation inDrosophila melanogasterReveals Genes Associated withCoxiella burnetiiInfection
Authors: Guzman Rosa M. , Howard Zachary P. , Liu Ziying , Oliveira Ryan D. , Massa Alisha T. , Omsland Anders , White Stephen N. , Goodman Alan G.
Published: May 2020

The gram-negative bacteriumCoxiella burnetiiis the causative agent of Query (Q) fever in humans and coxiellosis in livestock. Association between host genetic background andCoxiella burnetiipathogenesis has been demonstrated both in humans and animals; however, specific genes associated with severity of infection remain unknown. We employed theDrosophilaGenetics Reference Panel to perform a genome-wide association study and identify host genetic variants that affectCoxiella burnetiiinfection outcome. The analysis resulted in 64 genome-wide suggestive (P < 10−5) single nucleotide polymorphisms or gene variants in 25 unique genes. We examined the role of each gene inCoxiella burnetiiinfection using flies carrying a null mutation or RNAi knockdown of each gene and monitoring survival. Of the 25 candidate genes, 15 validated using at least one method. For many, this is the first report establishing involvement of these genes or their homologs withCoxiella burnetiisusceptibility in any system. Among the validated genes,FERandtaraplay roles in the JAK-STAT, JNK, and decapentaplegic/TGF-β signaling pathways that are associated with the innate immune response toCoxiella burnetiiinfection. Two other two validated genes,CG42673andDIP-ɛ, play roles in bacterial infection and synaptic signaling but no previous association withCoxiella burnetiipathogenesis. Furthermore, since the mammalian ortholog ofCG13404(PLGRKT) is an important regulator of macrophage function,CG13404could play a role inCoxiella burnetiisusceptibility through hemocyte regulation. These insights provide a foundation for further investigation of genetics ofCoxiella burnetiisusceptibility across a wide variety of hosts.
BRAFV600Einduces reversible mitotic arrest in human melanocytes via microRNA-mediated suppression of AURKB
Authors: McNeal Andrew S. , Belote Rachel L. , Zeng Hanlin , Urquijo Marcus , Barker Kendra , Torres Rodrigo , Curtin Meghan , Shain A. Hunter , Andtbacka Robert H. I. , Holmen Sheri L. , Lum David H. , McCalmont Timothy H. , VanBrocklin Matthew W. , Grossman Douglas , Wei Maria L. , Lang Ursula E. , Judson-Torres Robert L.
Published: May 2020

Benign melanocytic nevi frequently emerge when an acquiredBRAFV600Emutation triggers unchecked proliferation and subsequent arrest in melanocytes. Recent observations have challenged the role of oncogene-induced senescence in melanocytic nevus formation, necessitating investigations into alternative mechanisms for the establishment and maintenance of proliferation arrest in nevi. We compared the transcriptomes of melanocytes from healthy human skin, nevi, and melanomas arisen from nevi and identified a set of microRNAs as highly expressed nevus-enriched transcripts. Two of these microRNAs – MIR211-5p and MIR328-3p – induced mitotic failure, genome duplication and proliferation arrest in human melanocytes through convergent targeting of AURKB. We demonstrate thatBRAFV600Einduces a similar proliferation arrest in primary human melanocytes that is both reversible and conditional. Specifically,BRAFV600Eexpression stimulates either arrest or proliferation depending on the differentiation state of the melanocyte. We report genome duplication in human melanocytic nevi, reciprocal expression of AURKB and microRNAs in nevi and melanomas, and rescue of arrested human nevus cells with AURKB expression. Together, our data describe an alternative molecular mechanism for melanocytic nevus formation that is congruent with both experimental and clinical observations.
Effect of leaf temperature on estimating physiological traits of wheat leaves from hyperspectral reflectance
Authors: Khan Hammad A , Nakamura Yukiko , Furbank Robert T , Evans John R
Published: May 2020

A growing number of leaf traits can be predicted from hyperspectral reflectance data. These include structural and compositional traits, such as leaf mass per area, nitrogen and chlorophyll content, but also physiological traits such a Rubisco carboxylation activity, electron transport rate and respiration rate. Since physiological traits vary with leaf temperature, how does this impact on predictions made from reflectance measurements? We investigated this with two wheat varieties, by repeatedly measuring each leaf through a sequence of temperatures imposed by varying the air temperature in a growth room. The function predicting Rubisco capacity normalised to 25 °C predicted the same value, regardless of leaf temperatures ranging from 20 to 35°C. Leaf temperature affected none of the predicted traits: Vcmax25, J, chlorophyll content, LMA, N content per unit leaf area or Vcmax25/N. However, as others have derived models to predict Rubisco activity that includes variation associated with leaf temperature, we discuss whether these functions may include a temperature signal within the reflectance spectra.
Hidden components of microbiome diversity revealed by cell wall lysis with Adaptive Focused Acoustics
Authors: Wallace Giselle F. , Ahluwalia Sonia , Thovarai Vishal , Laugharn James , Khoja Hamid , Sen Shurjo K.
Published: May 2020

Within the rapidly evolving field of microbiome sequencing, a primary need exists for experimentally capturing microbiota in a manner as close as possible to theirin vivocomposition. During microbiome profiling, the first step necessarily involves lysis of the cell wall, releasing nucleic acids for next-generation sequencing. Microbial cell wall thicknesses can vary between 5nm to 80nm; while some species are quite easy to lyse, others are particularly resistant to lysis. Despite this, current chemical/mechanical lysis protocols ignore the possibility that species with different cell wall thicknesses are lysed at differential rates. This creates noise in species compositions and possibly skews current microbiome results in ways that are not currently understood. To develop a cell wall thickness-agnostic lysis protocol, we used Adaptive Focused Acoustics (AFA), a tunable acoustic methodology for processing of biological samples. Using identical aliquots of mouse stool homogenate as the lysis substrate, we compared AFA with chemical/mechanical lysis methodology routinely used in microbiome studies and found that AFA-mediated lysis substantially increases both microbial DNA yield as well as alpha and beta diversity. By starting with lower AFA energy levels, sequentially removing aliquots at each step, and subjecting the remainder to progressively stronger AFA treatment, we developed a sequential lysis method that accounts for differences in cell wall thickness. This method revealed even greater levels of diversity than single-timepoint AFA treatment. 16S sequencing results from the above experiments were verified by shotgun metagenome sequencing of a subset of the AFA samples. We found that lysis-induced noise affects not just species compositaions, but also functional characterization of shotgun metagenome data. AFA samples also showed a higher detection of eukaryotic and fungal DNA. We suggest that AFA-mediated lysis produces a truer representation of the native microbiota, and that this method deserves consideration as a potential addition to microbiome lysis protocols.
Antihypertensive medication uses and serum ACE2 levels
Authors: Emilsson Valur , Gudmundsson Elias F. , Aspelund Thor , Jonsson Brynjolfur G. , Gudjonsson Alexander , Launer Lenore J. , Jennings Lori L. , Gudmundsdottir Valborg , Gudnason Vilmundur
Published: May 2020

Importance

Recent reports have shown that hypertension is the most common comorbidity associated with mortality in the current coronavirus disease 2019 (COVID-19). This has been related to the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) as animal studies indicate that these medications increase levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2. This has prompted clinicians to recommend discontinuing ACEIs and ARBs.

Objective

To examine the effect of ACEIs or ARBs treatment on serum levels of ACE2 and other key enzymes in the renin-angiotensin system (RAS).

Design, Setting, and Participants

A single center population-based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS) of the elderly (mean age 75±6 years) stratified by ACEIs (N = 699) or ARBs (N = 753) treatment.

Main Outcomes and Measures

The AGES-RS study population was stratified by ACEIs and ARBs medication use and compared for age, body mass index (BMI) (kg/m2), hypertension and type 2 diabetes (T2D) as well as serum levels of renin, ACE and ACE2.

Results

While renin and ACE levels were significantly raised in serum of individuals on ACEIs or ARBs treatments, the ACE2 levels remained unaffected.

Conclusions and Relevance

Treatment with ACEIs or ARBs does not raise ACE2 levels in serum. Therefore, the present study does not support the proposed discontinuation of these medications among patients affected with COVID-19.

Key Points

Question

Does treatment with the antihypertensive medications angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) result in elevated levels of the cellular receptor for the coronavirus SARS-CoV-2, ACE2?

Findings

In a single center population-based cohort (AGES-RS), 699 and 753 individuals were either on ACEIs or ARBs treatment, respectively. The serum levels of the key enzymes in the renin-angiotensin system (RAS), renin, ACE and ACE2 were measured in 5457 subjects of the AGES-RS and their serum levels in individuals on ACEIs or ARBs treatment compared to those not using these medications. While renin and ACE were significantly raised in serum of ACEIs and ARBs users, the levels of ACE2 remained unaffected.

Meaning

These results do not support the proposed routine discontinuation of ACEIs or ARBs among patients affected with COVID-19.
Hydroxychloroquine and Tocilizumab Therapy in COVID-19 Patients – An Observational Study
Authors: Ip Andrew , Berry Donald A. , Hansen Eric , Goy Andre H. , Pecora Andrew L , Sinclaire Brittany A , Bednarz Urszula , Marafelias Michael , Berry Scott M. , Berry Nicholas S. , Mathura Shivam , Sawczuk Ihor S , Biran Noa , Go Ronaldo C , Sperber Steven , Piwoz Julia A , Balani Bindu , Cicogna Cristina , Sebti Rani , Zuckerman Jerry , Rose Keith M , Tank Lisa , Jacobs Laurie G , Korcak Jason , Timmapuri Sarah L. , Underwood Joseph P. , Sugalski Gregory , Barsky Carol , Varga Daniel W. , Asif Arif , Landolfi Joseph C , Goldberg Stuart L
Published: May 2020

Background

Hydroxychloroquine has been touted as a COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has been proposed as a treatment of critically ill patients.

Objective

To describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients.

Design

Retrospective observational cohort study of electronic health records Setting: 13-hospital network spanning the state of New Jersey.

Participants

Patients hospitalized between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020.

Main Outcomes

The primary outcome was death.

Results

Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%.

Conclusions

This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials.

Trial Registration

Clinicaltrials.gov Identifier: NCT04347993
Comparison of horizontal corneal diameter measurements using Orbscan IIz, OPD Scan III, and IOLMaster 700
Authors: Cruz Sebastian , Valenzuela Felipe , Stoppel Juan , Maul Eugenio , Gibbons Allister
Published: May 2020

Purpose

To compare 3 automated devices for measuring the horizontal corneal diameter [white-to-white (WTW) distance].

Setting

Fundacion Oftalmologica Los Andes, Santiago, Chile.

Study Design

Retrospective.

Methods

In 65 eyes of 38 patients, the WTW distance was measured independently using Orbscan IIz tomography system (Bausch & Lomb), IOLMaster 700 (Carl Zeiss Meditec) and OPD Scan III (NIDEK). We tested for systematic differences in measurements and estimated the limits of agreement (LoA) using linear mixed effects models.

Results

The mean WTW distance was 11.8 ± 0.40 mm with Orbscan IIz, 12.1 ± 0.5 mm with IOLMaster 700 and 12.0 ± 0.4 mm with OPD Scan III. The mean difference between IOLMaster 700 and Orbscan IIz was 0.33 (95% CI 0.28;0.38) (p<0.001), between OPD Scan III and Orbscan IIz was 0.24 mm (95% CI 0.21;0.28) (p<0.001), and between IOL Master 700 and OPD Scan III was 0.09 (95% CI 0.05;0.12) (p<0.001). The 95% LoA for Orbscan IIz versus IOLMaster 700 was −0.69 mm to 0.03 mm, Orbscan IIz versus OPD Scan III was −0.52 mm to −0.03 mm, and OPD versus IOLMaster 700 was −0.39 mm to 0.22 mm. Switching to IOLMaster 700 or OPD Scan III measurements led to a selection of a longer phakic IOL length (Visian ICL, STAAR) in 34% and 33% of the cases, respectively compared to Orbscan IIz.

Conclusions

The data suggests that these devices are not interchangeable for usual clinical practice. Adjustments based on mean differences was not enough to compensate for inter-instrument discrepancy in WTW measurements.
Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells
Authors: Russell John Parkin , Lim Xinhong , Santambrogio Alice , Yianni Val , Kemkem Yasmine , Wang Bruce , Fish Matthew , Haston Scott , Grabek Anaëlle , Hallang Shirleen , Lodge Emily Jane , Patist Amanda Louise , Schedl Andreas , Mollard Patrice , Nusse Roeland , Andoniadou Cynthia Lilian
Published: May 2020

In response to physiological demand, the pituitary gland generates new hormone-secreting cells from committed progenitor cells throughout life. It remains unclear to what extent pituitary stem cells (PSCs), which uniquely express SOX2, contribute to pituitary growth and renewal. Moreover, neither the signals that drive proliferation nor their sources have been elucidated. We have used genetic approaches in the mouse, showing that the WNT pathway is essential for proliferation of all lineages in the gland. We reveal that SOX2+stem cells are a key source of WNT ligands. By blocking secretion of WNTs from SOX2+PSCsin vivo, we demonstrate that proliferation of neighbouring committed progenitor cells declines, demonstrating that progenitor multiplication depends on the paracrine WNT secretion from SOX2+PSCs. Our results indicate that stem cells can hold additional roles in tissue expansion and homeostasis, acting as paracrine signalling centres to coordinate the proliferation of neighbouring cells.
Development of new cowpea (Vigna unguiculata) mutant genotypes, analysis of their agromorphological variation, genetic diversity and Population structure
Authors: Diouf Made , Diallo Sara , Badiane François Abaye , Diack Oumar , Diouf Diaga
Published: May 2020

Cowpea is one of the most important legume grain in the SubSaharian region of Africa used for human consumption and animal feeding but its production is hampered by biotic and abiotic constraints raising the need to broaden its genetic basis. For this purpose, the seeds of two cowpea varieties Melakh and Yacine were respectively irradiated with 300 and 340 Gy. The developed mutant populations were agromorphologically characterized from M5 to M7 while the genetic diversity of the last were evaluated using 13 ISSR markers. Based on agromorphological characterization, variation of flower color, pod length, seed coat color and seed weight with respectively 78.01, 68.29, 94.48 and 57.58% heritability were recorded in the mutant lines. PCA analyses allowed to identify the elite mutants based on their agromorphological traits while Pearson’s correlation results revealed a positive correlation between yield component traits. Three subpopulations were identified through STRUCTURE analyses but assignment of the individuals in each group was improved using DAPC. Analysis of Molecular Variance revealed that the majority (85%) of the variance rather existed within group than among (15%) group. Finally, our study allowed to select new promising mutant genotypes which could be tested for multi local trials to evaluate their agronomic performance.
Excitatory-Inhibitory Balance within EEG Microstates and Resting-state fMRI Networks: Assessed via Simultaneous PET-MR-EEG Imaging
Authors: Rajkumar R , Régio Brambilla C , Veselinović T , Bierbrier J , Wyss C , Ramkiran S , Orth L , Lang M , Rota Kops E , Mauler J , Scheins J , Neumaier B , Ermert J , Herzog H , Langen KJ , Binkofski F , Lerche C , Shah NJ , Neuner I
Published: May 2020

The symbiosis of neuronal activities and glucose energy metabolism is reflected in the generation of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) signals. However, their association with the balance between neuronal excitation and inhibition (E/I-B), which is closely related to the activities of glutamate and GABA (γ -aminobutyric acid) and the receptor availability (RA) of GABAAand mGluR5, remains unexplored. This study investigates these associations during the resting state (RS) condition using simultaneously recorded PET/MR/EEG (trimodal) data. Glucose metabolism and neuroreceptor binding availability (non-displaceable binding potential (BPND)) of GABAAand mGluR5 were found to be significantly higher and closely linked within core resting-state networks (RSNs). The neuronal generators of EEG microstates and the fMRI measures were most tightly associated with the BPNDof GABAArelative to mGluR5 BPNDand the glucose metabolism, emphasising a predominance of inhibitory processes within in the core RSNs at rest.
Clinical and molecular characterization of COVID-19 hospitalized patients
Authors: Benetti Elisa , Giliberti Annarita , Emiliozzi Arianna , Valentino Floriana , Bergantini Laura , Fallerini Chiara , Anedda Federico , Amitrano Sara , Conticini Edoardo , Tita Rossella , d’Alessandro Miriana , Fava Francesca , Marcantonio Simona , Baldassarri Margherita , Bruttini Mirella , Mazzei Maria Antonietta , Montagnani Francesca , Mandalà Marco , Bargagli Elena , Furini Simone ,   COVID-19 MULTICENTER STUDY, Renieri Alessandra , Mari Francesca
Published: May 2020

Clinical and molecular characterization by Whole Exome Sequencing (WES) is reported in 35 COVID-19 patients attending the University Hospital in Siena, Italy, from April 7 to May 7, 2020. Eighty percent of patients required respiratory assistance, half of them being on mechanical ventilation. Fiftyone percent had hepatic involvement and hyposmia was ascertained in 3 patients. Searching for common genes by collapsing methods against 150 WES of controls of the Italian population failed to give straightforward statistically significant results with the exception of two genes. This result is not unexpected since we are facing the most challenging common disorder triggered by environmental factors with a strong underlying heritability (50%). The lesson learned from Autism-Spectrum-Disorders prompted us to re-analyse the cohort treating each patient as an independent case, following a Mendelian-like model. We identified for each patient an average of 2.5 pathogenic mutations involved in virus infection susceptibility and pinpointing to one or more rare disorder(s). To our knowledge, this is the first report on WES and COVID-19. Our results suggest a combined model for COVID-19 susceptibility with a number of common susceptibility genes which represent the favorite background in which additional host private mutations may determine disease progression.
Sensory stimulation enhances phantom limb perception and movement decoding
Authors: Osborn Luke E. , Ding Keqin , Hays Mark A. , Bose Rohit , Iskarous Mark M. , Dragomir Andrei , Tayeb Zied , Lévay György M. , Hunt Christopher L. , Cheng Gordon , Armiger Robert S. , Bezerianos Anastasios , Fifer Matthew S. , Thakor Nitish V.
Published: May 2020

Objective

A major challenge for controlling a prosthetic arm is communication between the device and the user’s phantom limb. We show the ability to enhance amputees’ phantom limb perception and improve movement decoding through targeted transcutaneous electrical nerve stimulation (tTENS).

Approach

Transcutaneous nerve stimulation experiments were performed with four amputee participants to map phantom limb perception. We measured myoelectric signals during phantom hand movements before and after amputees received sensory stimulation. Using electroencephalogram (EEG) monitoring, we measure the neural activity in sensorimotor regions during phantom movements and stimulation. In one participant, we also tracked sensory mapping over 2 years and movement decoding performance over 1 year.

Main results

Results show improvements in the amputees’ ability to perceive and move the phantom hand as a result of sensory stimulation, which leads to improved movement decoding. In the extended study with one amputee, we found that sensory mapping remains stable over 2 years. Remarkably, sensory stimulation improves within-day movement decoding while performance remains stable over 1 year. From the EEG, we observed cortical correlates of sensorimotor integration and increased motor-related neural activity as a result of enhanced phantom limb perception.

Significance

This work demonstrates that phantom limb perception influences prosthesis control and can benefit from targeted nerve stimulation. These findings have implications for improving prosthesis usability and function due to a heightened sense of the phantom hand.
Analysis of the increase in cross-sectional area of the median nerve and its relation to age in neonates, infants and children using high-resolution ultrasound imaging
Authors: Jenny Carole , Lütschg Jürg , Broser Philip J.
Published: May 2020

AIM

To analyze the increase in the cross-sectional area (CSA) of the median nerve during early childhood.

METHOD

This prospective, cross-sectional study used high-resolution ultrasound images of the median nerve from three locations (wrist, forearm and upper arm). A total of 43 participants (32 of whom were children younger than 2 years) were included in the study.

RESULTS

A strong and highly significant correlation was found between age and CSA (r = 0.8, p < 0.0001). The growth rate of CSA decreases with age. The increase in CSA follows a logarithmic growth curve (p < 0.0001). Based on the regression analysis, an age-synchronous increase in CSA for all three locations was found. The nerve reaches 70% of its final CSA by 2 years of age.

INTERPRETATION

Similar to the nerve conduction speed, the increase in CSA is greatest during the first 2 years of life. Then, the rate gradually and synchronously slows at the proximal and distal locations.

What this paper adds

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Normative values for increased cross-sectional area (CSA) of the median nerve.

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Standardized locations and image procedures outlined for the clinical setting.

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Growth dynamic of the CSA of the median nerve in children.

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Normative data for development of the median nerve in children.

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High resolution ultrasound images of the maturating median nerve in neonates, infants and children.
Low Covid-19 hospitalisation in Dumfries and Galloway: comparison with other Scottish health boards
Authors: Rideout Andrew , Murray Calum , Isles Chris
Published: May 2020

Background

Covid-19 virus activity appears to have affected some parts of the United Kingdom more than others. Dumfries and Galloway (D&G) has seen fewer hospitalised cases than predicted. We wondered whether this might be related at least in part to population density.

Methods

We compared Covid-19 hospitalisation rates/100,000 population in D&G with those of the other 10 mainland Scottish health boards. We chose two time points: 19th April which was the peak of the pandemic in Scotland and 15th May, seven and a half weeks after lockdown. We used chi square and odds ratios with 95% confidence intervals to test for differences in hospitalisation rates and Pearson’s correlation coefficient to examine the relation between hospitalisation rates and population density. Population density for each health board was provided by National Records of Scotland.

Results

Hospitalisation in D&G was 13.4/100,000 on 19th April, falling to 1.3/100,000 by 15th May. Corresponding hospitalisation rates in Greater Glasgow & Clyde (GGC) were 50.1/100,000 and 38.9/100,000. Compared to GGC, hospitalisation rates in D&G were 3 times lower at peak (OR 0.27, 95% CI 0.17, 0.42) and 30 times lower by 15th May (OR 0.03, 95% CI 0.01, 0.14). Hospitalisation rates for the other health boards lay in between values recorded for D&G and GGC and fell in 10 of the 11 boards between these two dates. There was a positive association between hospitalisation rate and population density (r=0.756, p=0.007 on 19th April and r=0.840, p<0.001 for 15th May).

Conclusion

We have confirmed there are large differences in Covid-19 hospitalisation rates across the 11 mainland Scottish health boards, that are in part related to population density. These data support a regional rather than one nation approach to easing Covid-19 restrictions.