bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of neonates after postpartum discharge and all children in the ambulatory setting during the coronavirus disease 2019 (COVID-19) pandemic
Authors: Harriel Katherine L. , Nolt Dawn , Moore Scot , Kressly Susan , Bernstein Henry (Hank)
Published: July 2020

Purpose of review

The present coronavirus disease 2019 (COVID-19) pandemic has created additional challenges with an increased number of presumed healthy, full-term newborns being discharged at 24 h after delivery. Short lengths of stay raise the possibility of mother–infant dyads being less ready for discharge, defined as at least one of the three informants (i.e., mother, pediatrician, and obstetrician) believing that either the mother and/or infant should stay longer than the proposed time of discharge. This public health crisis has reduced the number of in-person well child visits, negatively impacting vaccine receipt, and anticipatory guidance.

Recent findings

Extra precautions should be taken during the transition period between postpartum discharge and follow-up in the ambulatory setting to ensure the safety of all patients and practice team members. This should include restructuring office flow by visit type and location, limiting in-person visits during well infant exams, instituting proper procedures for personal protective equipment and for cleaning of the office, expanding telehealth capabilities for care and education, and prioritizing universal vaccinations and routine well child screenings.

Based on current limited evidence, this report provides guidance for the postdischarge management of newborns born to mothers with confirmed or suspected disease in the ambulatory setting as well as prioritizing universal immunizations and routine well child screenings during the COVID-19 pandemic.
Knowledge Gaps in the Etiology and Pathophysiology of Incontinence-Associated Dermatitis
Authors: Koudounas Sofoklis , Bader Dan L. , Voegeli David
Published: July 2020

PURPOSE:

Incontinence-associated dermatitis (IAD) due to the prolonged exposure of the skin to urinary, fecal, or double incontinence represents a major clinical practice challenge. The aim of this review was to identify and critically appraise the results of published studies on the etiology and pathophysiology of IAD and highlight the current gaps in empirical evidence.

METHODS:

Scoping literature review.

SEARCH STRATEGY:

The electronic databases PubMed, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, and Embase were searched for relevant articles published from 1996 to April 2018. Thirteen studies and review articles related to the etiology and pathophysiology of IAD were identified in our initial review, and 3 studies published subsequent to our initial review were evaluated and included in our final review.

FINDINGS:

These studies suggest that several etiologic factors contribute to the development of IAD including exposure to urine, stool, or a combination of these substances (dual incontinence), the duration and frequency of exposure, frequent cleaning, and inflammatory responses. Results from the current scoping review showed that despite the increasing interest in IAD, evidence related to the underlying mechanisms causing IAD remains sparse. This paucity represents a clear gap in knowledge and indicates a need for additional research.

IMPLICATIONS:

Future studies should aim at elucidating: (1) the role of urine and its inherent pH on skin integrity, (2) the role of stool, specific digestive enzymes, and fecal bacteria on skin integrity, (3) the permeability and susceptibility of the skin to damage following frequent cleansing activities and occlusion, and (4) the specific inflammatory response triggered following exposure to urine and fecal matter.
Low Risk of Variceal Bleeding Among Subjects With Cirrhosis Treated With Electroconvulsive Therapy
Authors: Ramsey Mitchell L. , Sobotka Lindsay A. , Hinton Alice , Reeves Kevin C. , Hanje Adam James
Published: July 2020

Background and Aim

Esophageal variceal bleeding is a dangerous complication of end-stage liver disease. There is limited information evaluating the hypothesis that medical procedures, specifically electroconvulsive therapy (ECT), may lead to variceal bleeding. The current study aims to determine the risk of variceal bleeding among subjects with cirrhosis who undergo ECT compared with other short medical procedures.

Methods

The Nationwide Inpatient Sample (2002–2013) and Nationwide Readmissions Database (2010–2014) were queried using International Classification of Disease, Ninth Revision, codes to evaluate all patients 18 years or older with cirrhosis who underwent ECT, bronchoscopy, or cystoscopy, or who experienced in-hospital seizures. Rates of variceal bleeding and hospital outcomes were compared. Multivariable analysis for readmission rate was performed.

Results

From the Nationwide Inpatient Sample, a total of 5,442,306 patients with cirrhosis were studied, including 840 (0.02%) patients who underwent ECT. Patients who underwent ECT were more likely to have compensated cirrhosis (P < 0.001). Among patients without ECT, 6.8% had variceal bleeding during admission compared with 0% who underwent ECT. From the Nationwide Readmissions Database, 1,383,853 patients were included, including 357 patients (0.03%) who underwent ECT during index admission. Electroconvulsive therapy did not increase the risk of 30- or 90-day readmission for variceal bleeding or mortality compared with other short medical procedures.

Conclusions

Electroconvulsive therapy does not increase the risk of variceal bleeding in subjects with compensated and decompensated cirrhosis. Preoperative optimization of these patients should take the risk of bleeding into account based on current guidelines for variceal surveillance.
Real-world Experience with Favipiravir for Treatment of COVID-19 in Thailand: Results from a Multicenter Observational Study
Authors: Rattanaumpawan Pinyo , Jirajariyavej Supunnee , Lerdlamyong Kanokorn , Palavutitotai Nattawan , Saiyarin Jatuporn
Published: July 2020

SYNOPSIS

Background

Favipiravir is a broad-spectrum oral antiviral agent that shows in vitro activity against SARS-CoV-2. Presently, data on the effectiveness and optimal dosage of favipiravir for treating COVID-19 is limited.

Methods

We conducted a retrospective observational study of hospitalized adult patients with COVID-19 at five tertiary care hospitals in Thailand. We reviewed patient charts to obtain all necessary data.

Results

Among 247 COVID-19 patients, 63 (23.0%) received ≥1 dose of favipiravir. Of these, 27.0% required an O2-nasal cannula, 9.5% required non-invasive ventilation and/or high-flow O2-therapy, and 6.4% required invasive mechanical ventilation and/or ECMO. The median baseline NEWS2 score was 5(0–16). The Day-7 clinical improvement rate [95%CI] was 66.7%[53.7–78.0%] in all patients, 92.5%[75.7%–99.1%] in patients who did not require O2-supplementation, and 47.2%[0.4%–64.5%] in patients who required O2-supplementation. No life-threatening adverse events were identified. The 28-day mortality rate was 4.8%.

Multivariate analysis revealed three poor prognostic factors for Day-7 clinical improvement [odds ratio (95%CI); p-value]: older age [0.94 (0.89–0.99); p=0.04], higher baseline NEWS2 score [0.64 (0.47–0.88); p=0.006], and lower favipiravir loading dose (≤45 mg/kg/day) [0.04 (0.005–0.4); p=0.006].

Conclusions

Our study reports the promising effectiveness of favipiravir for treating COVID-19 patients. In addition to older age and a high baseline NEWS2 score, a low loading dose of favipiravir (≤45 mg/kg/day) was also identified as a poor prognostic factor for early clinical improvement. Further studies to explore the optimal dose and the optimal timing of drug initiation for favipiravir should be performed.
Germination response of diverse wild and landrace chile peppers (Capsicumspp.) under drought stress simulated with polyethylene glycol
Authors: Bernau Vivian , Barbolla Lev Jardón , McHale Leah K. , Mercer Kristin L.
Published: July 2020

Responses to drought within a single species may vary based on plant development stage, drought severity, and the avoidance or tolerance mechanisms employed. Early drought stress can restrict emergence and seedling growth. Thus, in areas where water availability is limited, rapid germination leading to early plant establishment may be beneficial. Alternatively, germination without sufficient water to support the seedling may lead to early senescence, so reduced germination under low moisture conditions may be adaptive at the level of the population. We studied the germination response to osmotic stress of diverse chile pepper germplasm collected in southern Mexico from varied ecozones, cultivation systems, and of named landraces. Drought stress was simulated using polyethylene glycol solutions. Overall, survival time analysis revealed delayed germination at the 20% concentration of PEG across all ecozones. The effect was most pronounced in the genotypes from hotter, drier ecozones. Additionally, accessions from wetter and cooler ecozones had the fastest rate of germination. Moreover, accessions of the landracesCosteño RojoandTustagerminated more slowly and incompletely if sourced from a drier ecozone than a wetter one, indicating that slower, reduced germination under drought stress may be an adaptive avoidance mechanism. Significant differences were also observed between named landraces, with more domesticated types from intensive cultivation systems nearly always germinating faster than small-fruited backyard- or wild-types, perhaps due to the fact that the smaller-fruited accessions have generally undergone less selection. Thus, we conclude that there is evidence of local adaptation to both ecozone of origin and source cultivation system in germination characteristics of diverse chile peppers.
In-cell detection of conformational sub-states of a GPCR quaternary structure: Modulation of sub-state probability by cognate ligand binding
Authors: Paprocki Joel , Biener Gabriel , Stoneman Michael , Raicu Valerica
Published: July 2020

While the notion that G protein-coupled receptors (GPCRs) associate into homo- and hetero-oligomers has gained more recognition in recent years, a lack of consensus remains among researchers regarding the functional relevance of GPCR oligomerization. A relatively recent technique, Förster resonance energy transfer (FRET) spectrometry, allows for the determination of the oligomeric (or quaternary) structure of proteins in living cells via analysis of efficiency distributions of energy transferred from optically excited fluorescent tags acting as donors of energy to fluorescent tags acting as acceptors of energy and residing within the same oligomer. In this study, we significantly improved the resolution of the FRET-spectrometry approach to detect small differences between the interprotomeric distances among GPCR oligomers with subtle differences in quaternary structures. We then used this approach to study the conformational substates of oligomers of sterile 2 α-factor receptor (Ste2), a class D GPCR found in the yeastSaccharomyces cerevisiaeof mating typea. Ste2 has previously been shown to form tetrameric oligomers at relatively low expression levels (between 11 and 140 molecules/μm2) in the absence of its cognate ligand, the α-factor pheromone. The significantly improved FRET spectrometry technique allowed us to detect multiple distinct quaternary conformational substates of Ste2 oligomers, and to assess how the α-factor ligand altered the proportion of such substates. The ability to determine quaternary structure substates of GPCRs provides exquisite means to elucidate functional relevance of GPCR oligomerization.
Routine measurement of serum procalcitonin allows antibiotics to be safely withheld in patients admitted to hospital with SARS-CoV-2 infection
Authors: Williams Emma J. , Mair Luke , de Silva Thushan I. , Green Dan J. , House Philip , Cawthron Kay , Gillies Christopher , Wigfull James , Parsons Helena , Partridge David G.
Published: July 2020

Background

It can be a diagnostic challenge to identify COVID-19 patients without bacterial co-infection in whom antibiotics can be safely stopped. We sought to evaluate the validity of a guideline that recommends withholding antibiotics in patients with a low serum procalcitonin (PCT).

Methods

We retrospectively collected 28-day outcome data on patients admitted to Sheffield Teaching Hospitals NHS Foundation Trust, UK, between 5 March and 15 April 2020, with a positive SARS-CoV-2 polymerase chain reaction (PCR) and PCT within 48 hours of diagnosis. PCT was considered negative if ≤0.25ng/ml and positive if >0.25ng/ml. Primary outcomes included antibiotic consumption, mortality, intensive care admission and length of hospital stay.

Results

368 patients met the inclusion criteria; 218 (59%) had a negative PCT and 150 (41%) positive. At 48 hours post-diagnosis, 73 (33%) of those with a negative PCT were receiving antimicrobials compared to 126 (84%) with a positive PCT (p<0.001), with a corresponding reduction in antimicrobial usage over 28 days (median DDD of 3.0 vs 6.8 (p<0.001); median DOT 2 vs 5 days (p<0.001) between the negative and positive PCT groups.) In the negative PCT group, there were fewer deaths (62 (28%) vs. 54 (36%), (p=0.021)) and critical care admissions (19 (9%) vs. 28 (19%), (p=0.007)) than in the positive PCT group. Median length of hospital stay was 8.7 and 9 days in the negative and positive PCT groups respectively.

Conclusions

Procalcitonin is a valuable tool in the assessment of patients with SARS-CoV-2 infection, safely reducing the potential burden of unnecessary antibiotic usage.
Improved contiguity of the threespine stickleback genome using long-read sequencing
Authors: Nath Shivangi , Shaw Daniel E. , White Michael A.
Published: July 2020

While the cost and time for assembling a genome have drastically reduced, it still remains a challenge to assemble a highly contiguous genome. These challenges are rapidly being overcome by the integration of long-read sequencing technologies. Here, we use long sequencing reads to improve the contiguity of the threespine stickleback fish(Gasterosteus aculeatus)genome, a prominent genetic model species. Using Pacific Biosciences sequencing, we were able to fill over 76% of the gaps in the genome, improving contiguity over five-fold. Our approach was highly accurate, validated by 10X Genomics long-distance linked-reads. In addition to closing a majority of gaps, we were able to assemble segments of telomeres and centromeres throughout the genome. This highlights the power of using long sequencing reads to assemble highly repetitive and difficult to assemble regions of genomes. This latest genome build has been released through a newly designed community genome browser that aims to consolidate the growing number of genomics datasets available for the threespine stickleback fish.
PTBP1 promotes cardiac hypertrophy and diastolic dysfunction by modulating alternative splicing
Authors: Martí-Gómez Carlos , Larrasa-Alonso Javier , López-Olañeta Marina , Villalba-Orero María , García-Pavía Pablo , Sánchez-Cabo Fátima , Lara-Pezzi Enrique
Published: July 2020

Alternative splicing (AS) plays a major role in the generation of transcript diversity. In the heart, roles have been described for some AS variants and individual regulatory RNA binding proteins (RBPs); however, the global impact and regulation of AS patterns in cardiac pathophysiology is poorly understood. Here, we studied the AS profiles in heart disease, their relationship with heart development and the regulatory mechanisms control-ling AS dynamics in the mouse heart using a total of 136 RNA-seq samples. We found that AS and gene expression changes affect different genes, which are also involved in distinct biological functions. Developmental AS changes were more abundant and had stronger predicted impact on the encoded protein than those taking place during heart disease. However, AS changes in heart disease significantly modified protein interaction patterns and rewire the protein-protein interaction network. Using a database of experimentally determined binding sites of a large collection of RNA binding proteins, we studied the regulatory proteins associated to AS changes in each condition. Computational modelling revealed that developmental transitions were mainly driven by the up-regulation of MBNL1, whereas disease associated AS changes were driven by a more complex regulatory network, characterized by the interaction of different RNA binding proteins, with PTBP1 as the largest individual modulator. In adult mice, PTBP1 over-expression was sufficient to induce cardiac hypertrophy and diastolic dysfunction and significantly alter the AS profile. Overall, our study provides new in-sights into the functional impact of AS patterns in cardiac physiology and how computationally driven hypotheses can help to improve our understanding of RNA regulation and its contribution to heart disease.
The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases
Authors: Mäkinen Janne J. , Shin Yeonoh , Vieras Eeva , Virta Pasi , Metsä-Ketelä Mikko , Murakami Katsuhiko S. , Belogurov Georgiy A.
Published: July 2020

RNA polymerases (RNAPs) synthesize RNA from NTPs, whereas DNA polymerases synthesize DNA from 2’dNTPs. DNA polymerases select against NTPs by using steric gates to exclude the 2’ OH, but RNAPs have to employ alternative selection strategies. In single-subunit RNAPs, a conserved Tyr residue discriminates against 2’dNTPs, whereas selectivity mechanisms of multi-subunit RNAPs remain hitherto unknown. Here we show that a conserved Arg residue uses a two-pronged strategy to select against 2’dNTPs in multi-subunit RNAPs. The conserved Arg interacts with the 2’OH group to promote NTP binding, but selectively inhibits incorporation of 2’dNTPs by interacting with their 3’OH group to favor the catalytically-inert 2’-endo conformation of the deoxyribose moiety. This deformative action is an elegant example of an active selection against a substrate that is a substructure of the correct substrate. Our findings provide important insights into the evolutionary origins of biopolymers and the design of selective inhibitors of viral RNAPs.
How do biases in sex ratio and disease characteristics affect the spread of sexually transmitted infections?
Authors: Halimubieke Naerhulan , Pirrie Alistair , Székely Tamás , Ashby Ben
Published: July 2020

The epidemiology of sexually transmitted infections (STIs) is inherently linked to host mating dynamics. Studies across many taxa show that adult sex ratio, a major determinant of host mating dynamics, is often skewed - sometimes strongly - toward males or females. However, few predictions exist for the effects of skewed sex ratio on STI epidemiology, and none when coupled with sex biased disease characteristics. Here we use mathematical modelling to examine how interactions between sex ratio and disease characteristics affect STI prevalence in males and females. Notably, we find that while overall disease prevalence peaks at equal sex ratios, prevalence per sex peaks at skewed sex ratios. Furthermore, disease characteristics, sex-biased or not, drive predictable differences in male and female STI prevalence as sex ratio varies, with higher transmission and lower virulence generally increasing differences between the sexes for a given sex ratio. These findings may be due to a balance between increased per-capita mating in the less common sex, and a reduction in mating rate - hence disease prevalence - at the population level. Our work reveals new insights into how STI prevalence in males and females depends on a complex interaction between host population sex ratio and disease characteristics.
Analysis of Virus-Host Interactomes through a network-centric approach
Authors: Tradigo Giuseppe , Veltri Pierangelo , Guzzi Pietro Hiram
Published: July 2020

Abstract

Viruses are small microorganisms that invade living cells and use them to replicate themselves. Viruses cause many common human infections (such as cold flu) as well as many lethal diseases. Therefore the comprehensive knowledge of mechanisms used by viruses to infect living cells, also known as host-pathogen interactions, is crucial. Mechanisms of infections of viruses are mediated by Protein-protein interactions (PPIs). PPIs are often modelled using graphs, thus the use of such a model may also explain mechanisms of infection of viruses. In this work, we propose a methodology to model and analyse host-pathogen interactions and a supporting tool able to analyse such data. We also analyse host-pathogen interactions of some common viruses demonstrating common mechanism and differences.
Fourier spectral density of the coronavirus genome
Authors: Tan H.S.
Published: July 2020

We present an analysis of the coronavirus RNA genome via a study of its Fourier spectral density based on a binary representation of the nucleotide sequence. We find that at low frequencies, the power spectrum presents a small and distinct departure from the behavior expected from an uncorrelated sequence. We provide a couple of simple models to characterize such deviations. Away from a small low-frequency domain, the spectrum presents largely stochastic fluctuations about fixed values which vary inversely with the genome size generally. It exhibits no other peaks apart from those associated with triplet codon usage. We uncover an interesting, new scaling law for the coronavirus genome: the complexity of the genome scales linearly with the power-law exponent that characterizes the enveloping curve of the low-frequency domain of the spectral density.
Automated design of synthetic microbial communities
Authors: Karkaria Behzad D. , Fedorec Alex J. H. , Barnes Chris P.
Published: July 2020

In naturally occurring microbial systems, species rarely exist in isolation. There is strong ecological evidence for a positive relationship between species diversity and the functional output of communities. The pervasiveness of these communities in nature highlights that there may be advantages for engineered strains to exist in cocultures as well. Building synthetic microbial communities allows us to create distributed systems that mitigates issues often found in engineering a monoculture, especially when functional complexity is increasing. Here, we demonstrate a methodology for designing robust synthetic communities that use quorum sensing to control amensal bacteriocin interactions in a chemostat environment. We explore model spaces for two and three strain systems, using Bayesian methods to perform model selection, and identify the most robust candidates for producing stable steady state communities. Our findings highlight important interaction motifs that provide stability, and identify requirements for selecting genetic parts and tuning the community composition.
Inhibition of CMP-sialic acid transport by endogenous 5-methyl CMP
Authors: Ahuja Shivani , Cahill James , Hartfield Kimberly , Whorton Matthew R.
Published: July 2020

Nucleotide-sugar transporters (NSTs) transport nucleotide-sugar conjugates into the Golgi lumen where they are then used in the synthesis of glycans. We previously reported crystal structures of a mammalian NST, the CMP-sialic acid transporter (CST) (Ahuja and Whorton 2019). These structures elucidated many aspects of substrate recognition, selectivity, and transport; however, one fundamental unaddressed question is how the transport activity of NSTs might be physiologically regulated as a means to produce the vast diversity of observed glycan structures. Here, we describe the discovery that an endogenous methylated form of cytidine monophosphate (m5CMP) binds and inhibits CST. The presence of m5CMP in cells results from the degradation of RNA that has had its cytosine bases post-transcriptionally methylated through epigenetic processes. Therefore, this work not only demonstrates that m5CMP represents a novel physiological regulator of CST, but it also establishes a link between epigenetic control of gene expression and regulation of glycosylation.
MappingDrosophilainsulin receptor structure to the regulation of aging through analysis of amino acid substitutions
Authors: Yamamoto Rochele , Palmer Michael , Koski Helen , Curtis-Joseph Noelle , Tatar Marc
Published: July 2020

Genetic manipulations of theDrosophilainsulin/IGF signaling system slow aging, but it remains unknown how the insulin/IGF receptor acts to modulate lifespan or differentiate this control from that of growth, reproduction and metabolism. With homologous recombination we produced an allelic series of single amino acid substitutions in the fly insulin receptor (InR). Based on emerging biochemical and structural data, we map amino acid substitutions to receptor function to longevity and fecundity. We proposeInRmutants generate bias in the process of asymmetric transphosphorylation when the receptor is activated. This induces specific kinase subdomains that modulate lifespan by additive processes, one involving survival costs of reproduction and the other involving reproduction-independent systems of longevity assurance. We identify a mutant in the kinase insert domain that robustly extends lifespan without affecting growth or reproduction, suggesting this element controls aging through unique mechanisms of longevity assurance.
TADA – a Machine Learning Tool for Functional Annotation based Prioritisation of Putative Pathogenic CNVs
Authors: Hertzberg J. , Mundlos S. , Vingron M. , Gallone G.
Published: July 2020

The computational prediction of disease-associated genetic variation is of fundamental importance for the genomics, genetics and clinical research communities. Whereas the mechanisms and disease impact underlying coding single nucleotide polymorphisms (SNPs) and small Insertions/Deletions (InDels) have been the focus of intense study, little is known about the corresponding impact of structural variants (SVs), which are challenging to detect, phase and interpret. Few methods have been developed to prioritise larger chromosomal alterations such as Copy Number Variants (CNVs) based on their pathogenicity. We address this issue with TADA, a method to prioritise pathogenic CNVs through manual filtering and automated classification, based on an extensive catalogue of functional annotation supported by rigorous enrichment analysis. We demonstrate that our machine-learning classifiers for deletions and duplications are able to accurately predict pathogenic CNVs (AUC: 0.8042 and 0.7869, respectively) and produce a well-calibrated pathogenicity score. The combination of enrichment analysis and classifications suggests that prioritisation of pathogenic CNVs based on functional annotation is a promising approach to support clinical diagnostic and to further the understanding of mechanisms that control the disease impact of larger genomic alterations.
Dynamics of bacterial cell division: Z ring condensation is essential for cytokinesis
Authors: Squyres Georgia R. , Holmes Matthew J. , Barger Sarah R. , Pennycook Betheney R. , Ryan Joel , Yan Victoria T. , Garner Ethan C.
Published: July 2020

How proteins in the bacterial cell division complex (the divisome) coordinate to divide bacteria remains unknown. To explore how these proteins collectively function, we conducted a complete dynamic characterization of the proteins involved, and then examined the function of FtsZ binding proteins (ZBPs) and their role in cytokinesis. We find that the divisome consists of two dynamically distinct subcomplexes: stationary ZBPs that transiently bind to treadmilling FtsZ filaments, and a directionally-moving complex that includes cell wall synthases. FtsZ filaments treadmill at steady state and the ZBPs have no effect on filament dynamics. Rather, ZBPs bundle FtsZ filaments, condensing them into Z rings. Z ring condensation increases the recruitment of cell wall synthesis enzymes to the division site, and this condensation is necessary for cytokinesis.
Correlating cell function and morphology by performing fluorescent immunocytochemical staining on the light-microscope stage
Authors: Kawano Hiroyuki , Kakazu Yasuhiro , Iwabuchi Sadahiro , Harata N. Charles
Published: July 2020

Background

Correlation of fluorescence signals from functional changes in live cells with those from immunocytochemical indicators of their morphology following chemical fixation can be highly informative with regard to function-structure relationship. Such analyses can be technically challenging because they need consistently aligning the images between imaging sessions. Existing solutions include introducing artificial spatial landmarks and modifying the microscopes. However, these methods can require extensive changes to the experimental systems.

New method

Here we introduce a simple approach for aligning images. It is based on two procedures: performing immunocytochemistry while a specimen stays on a microscope stage (on-stage), and aligning images using biological structures as landmarks after they are observed with transmitted-light optics in combination with fluorescence-filter sets.

Results

We imaged a transient functional signal from a fluorescent Ca2+indicator, and mapped it to neurites based on immunocytochemical staining of a structural marker. In the same preparation, we could identify presynaptically silent synapses, based on a lack of labeling with an indicator for synaptic vesicle recycling and on positive immunocytochemical staining for a structural marker of nerve terminals. On-stage immunocytochemistry minimized lateral translations and eliminated rotations, and transmitted-light images of neurites were sufficiently clear to enable spatial registration, effective at a single-pixel level.

Comparison with existing methods

This method aligned images with minimal change or investment in the experimental systems.

Conclusions

This method facilitates information retrieval across multiple imaging sessions, even when functional signals are transient or local, and when fluorescent signals in multiple imaging sessions do not match spatially.
Do the Moroccan SARS-CoV-2 genetic diversity hamper the use of the developed universal vaccines in Morocco?
Authors: Laamarti Meriem , Essabbar Abdelomunim , Alouane Tarek , Kartti Souad , Boumajdi Nasma , Bendani Houda , Laamarti Rokia , Allam Loubna , Ouadghiri Mouna , Chemao-Elfihri M.W. , Ghrifi Fatima , Smyej Imane , Rahoui Jalila , Benrahma Houda , Diawara Idrissa , Aanniz Tarik , El Hafidi Naima , El Jaoudi Rachid , Nejjari Chakib , Amzazi Saaid , Mentag Rachid , Belyamani Lahcen , Ibrahimi Azeddine
Published: July 2020

The SARS-CoV-2 identified as coronavirus species associated with severe acute respiratory syndrome. At the time of writing, the genetic diversity of Moroccan strains of SARS-CoV-2 is poorly documented. The present study aims to analyze and identify the genetic variants of fortyeight Moroccan strains of SARS-CoV-2 collected from mid-March to the end of May and the prediction of their possible sources. Our results revealed 108 mutations in Moroccan SARS-CoV-2, 50% were non-synonymous were present in seven genes (S, M, N, E, ORF1ab, ORF3a, and ORF8) with variable frequencies. Remarkably, eight non-synonymous mutations were predicted to have a deleterious effect for (ORF1ab, ORF3a, and the N protein. The analysis of the haplotype network of Moroccan strains suggests different sources of SARS-CoV-2 infection in Morocco. Likewise, the phylogenetic analysis revealed that these Moroccan strains were closely related to those belonging to the five continents, indicating no specific strain dominating in Morocco. These findings have the potential to lead to new comprehensive investigations combining genomic data, epidemiological information, and clinical characteristics of SARS-CoV-2 patients in Morocco and could indicate that the developed vaccines are likely to be effective against Moroccan strains.
Pre-existing cutaneous conditions could increase the risk for SARS-COV-2 infection.
Authors: Xu Qiannan , Chen Lihong , Zhang Li , Hu Mengyan , Wang Xiaopan , Yang Qi , Le Yunchen , Xue Feng , Li Xia , Zheng Jie
Published: July 2020

Since the end of 2019, COVID-19 pandemic caused by the SARS-CoV-2 emerged globally. The angiotensin-converting enzyme 2 (ACE2) on the cell surface is crucial for SARS-COV-2 entering into the cells. We use SARS-COV-2 pseudo virus and humanized ACE2 mice to mimic the possible transmitting of SARS-COV-2 through skin based on the data we found that skin ACE2 level is associated with skin pre-existing cutaneous conditions in human and mouse models and inflammatory skin disorders with barrier dysfunction increased the penetration of topical FITC conjugated spike protein into the skin. Our study indicated the possibility that the pre-existing cutaneous conditions could increase the risk for SARS-COV-2 infection.
Step-wise increases inFT1expression regulate seasonal progression of flowering in wheat (Triticum aestivumL.)
Authors: Gauley Adam , Boden Scott A.
Published: July 2020

Flowering is regulated by genes that respond to changing daylengths and temperature, which have been well-studied using controlled conditions; however, the molecular processes underpinning flowering in nature remain poorly understood. Here, we investigate the genetic pathways that coordinate flowering and inflorescence development of wheat as daylengths extend naturally in the field, using lines that contain variant alleles for the key photoperiod gene,Photoperiod-1(Ppd-1). We found flowering involves a step-wise increase in the expression ofFLOWERING LOCUS T1(FT1), which initiates under day-neutral conditions of early spring. The incremental rise inFT1expression is overridden in plants that contain a photoperiod-insensitive allele ofPpd-1, which hastens the completion of spikelet development and accelerates flowering time. The accelerated inflorescence development of photoperiod-insensitive lines is promoted by advanced seasonal expression of floral meristem identity genes. The completion of spikelet formation is promoted byFLOWERING LOCUS T2, which regulates spikelet number and is activated byPpd-1. In wheat, flowering under natural photoperiods is regulated by step-wise increases in the expression ofFT1, which responds dynamically to extending daylengths to promote early inflorescence development. This research provides a strong foundation to improve yield potential by fine-tuning the photoperiod-dependent control of inflorescence development.
A head-mounted multi-camera system for electrophysiology and behavior in freely-moving mice
Authors: Sattler Nicholas , Wehr Michael
Published: July 2020

Advances in the ability to monitor freely-moving mice may prove valuable for the study of behavior and its neural correlates. Here we describe a head-mounted multi-camera system for mice, comprised of inexpensive miniature analog camera modules. We illustrate the use of this system with several natural behaviors including prey capture, courtship, jumping, and exploration. With a four-camera headset, monitoring the eyes, ears, whiskers, rhinarium, and binocular visual field can all be achieved simultaneously with high-density electrophysiology. With appropriate focus and positioning, all eye movements can be captured, including cyclotorsion. For studies of vision and eye movements, cyclotorsion provides the final degree of freedom required to reconstruct the visual scene in retinotopic coordinates or to investigate the vestibulo-ocular reflex in mice. Altogether, this system allows for comprehensive measurement of freely-moving mouse behavior, enabling a more holistic and multimodal approach to investigate ethological behaviors and other processes of active perception.
Quantifying the impact of US state non-pharmaceutical interventions on COVID-19 transmission
Authors: Korevaar Hannah M. , Becker Alexander D. , Miller Ian F. , Grenfell Bryan T. , Metcalf C. Jessica E. , Mina Michael J.
Published: July 2020

COVID-19 is an ongoing public health emergency. Without a vaccine or effective antivirals, non-pharmaceutical interventions form the foundation of current response efforts. Quantifying the efficacy of these interventions is crucial. Using mortality data and a classification guide of state level responses, we relate the intensity of interventions to statistical estimates of transmission, finding that more stringent control measures are associated with larger reductions in disease proliferation. Additionally, we observe that transmission increases with population density, but not population size. These results may help inform future response efforts.
ClinSV: Clinical grade structural and copy number variant detection from whole genome sequencing data
Authors: Minoche Andre E , Lundie Ben , Peters Greg B , Ohnesorg Thomas , Pinese Mark , Thomas David M , Zankl Andreas , Roscioli Tony , Schonrock Nicole , Kummerfeld Sarah , Burnett Leslie , Dinger Marcel E , Cowley Mark J
Published: July 2020

Whole genome sequencing (WGS) has the potential to outperform clinical microarrays for the detection of structural variants (SV) including copy number variants (CNVs), but has been challenged by high false positive rates. Here we present ClinSV, a WGS based SV integration, annotation, prioritisation and visualisation method, which identified 99.8% of pathogenic ClinVar CNVs >10kb and 11/11 pathogenic variants from matched microarrays. The false positive rate was low (1.5–4.5%) and reproducibility high (95–99%). In clinical practice, ClinSV identified reportable variants in 22 of 485 patients (4.7%) of which 35–63% were not detectable by current clinical microarray designs.
Social-distancing effectiveness tracking of the COVID-19 hotspot Stockholm
Authors: Oberhammer Joachim
Published: July 2020

Background

The COVID-19 outbreak in Stockholm, Sweden, is characterized by a near-absence of governmental interventions and high fatalities in the care home population. This study analyses the outbreak and the social-distancing effectiveness timeline in the general population and the care homes.

Methods

A novel distributed-compartmental, time-variant epidemiological model was designed specifically for COVID-19 transmission characteristics, featuring a/pre/symptomatic transmission, a non-linear hospital model, a weakly-coupled sub-model for the care-home population, and parametrized continuous social-distancing functions. The model parameters and the social-distancing timelines are determined by randomization and Monte-Carlo simulations analysing real-world data.

Findings

Despite a high initial reproduction number (3·29) and the near-absence of governmental interventions, the model quantitated that the transmission rate in the general population was suppressed by 73%, and in the care homes by 79%. The measures in the care homes took effect 4·8 days delayed; and if applied 4 or 8 days earlier, the fatalities could have been reduced by 63·2% or 89·9%. The infected population is estimated to 16·2% (June 10). An expected underestimation of population immunity by antibody studies is confirmed. The infection fatality ratio extrapolates to 0·61% (peak: 1·34%). The model indicates a seasonal effect which effectively suppressed a new rise. An analysed large-scale public event had no large influence. The asymptomatic ratio was determined to 35%.

Interpretation

The proposed model and methods have proven to analyse a COVID-19 outbreak and to re-construct the social-distancing behaviour with unprecedented accuracy, confirming even minor details indicated by mobility-data analysis, and are applicable to other regions and other emerging infectious diseases of similar transmission characteristics. The self-regulation of the population in Stockholm, influenced by advices by the authorities, was able to suppress a COVID-19 outbreak to a level far beyond that the stringency index of governmental interventions suggests. Proper timing of effective measures in the care homes is important to reduce fatalities.
APOE4 Copy Number-Dependent Proteomic changes in the Cerebrospinal Fluid
Authors: Berger Miles , Cooter Mary , Roesler Alexander S. , Chung Stacey , Park John , Modliszeski Jennifer L. , VanDusen Keith W. , Thompson J. Will , Moseley Arthur , Devinney Michael J. , Smani Shayan , Hall Ashley , Cai Victor , Browndyke Jeffrey N. , Lutz Michael W. , Corcoran David L. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: July 2020

Background

APOE4 has been hypothesized to increase Alzheimer’s disease risk by increasing neuroinflammation, though the specific neuroinflammatory pathways involved are unclear.

Objectives

To characterize CSF proteomic changes as a function of APOE4 copy number.

Methods

We analyzed targeted proteomic data obtained on ADNI CSF samples using a linear regression model adjusting for age, sex, and APOE4 copy number, and a second linear model also adjusting for AD clinical status. False Discovery Rate (FDR) was used to correct for multiple comparisons.

Results

In the first model, increasing APOE4 copy number was associated with significant expression decreases in a CRP peptide (q=0.006), and significant expression increases in peptides from ALDOA, CH3L1 (YKL-40), and FABPH (q<0.05 for each). In the second model (controlling for age, sex, and AD clinical status), increasing APOE4 copy number was associated with significant expression decreases in a CRP peptide (q=0.009). In both models, increased APOE4 copy number was associated with trends towards lower expression of all 24 peptides from all 8 different complement proteins measured here, although none of these differences were statistically significant. The odds of this happening by chance for 24 unrelated peptides would be less than 1 in 16 million.

Conclusions

Increasing APOE4 copy number was associated with decreased CSF CRP levels and increased CSF ALDOA, CH3L1 and FABH levels; the CRP decrease remained significant after controlling for AD clinical status. Increased APOE4 copy number may also be associated with decreased CSF complement pathway protein levels, a hypothesis for investigation in future studies.
Discriminating cognitive performance using biomarkers extracted from linear and nonlinear analysis of EEG signals by machine learning
Authors: Shivabalan K R , Brototo Deb , Shivam Goel , Sivanesan S
Published: July 2020

Nonlinear dynamics and chaos theory are being widely used nowadays in neuroscience to characterize complex systems within which the change of the output isn’t proportional to the change of the input. Nonlinear systems compared to linear systems, often appear chaotic, unpredictable, or counterintuitive, and yet their behaviour isn’t random. The importance of the time series analysis, which exhibits a typical complex dynamics, within the area of nonlinear analysis can’t be undermined. Hidden important dynamical properties of the physiological phenomenon can be detected by many features of these approaches. Nonlinear dynamics and chaos theory are being employed in neurophysiology with the aim to elucidate the complex brain activity from electroencephalographic (EEG) signals. The brain is a chaotic dynamical system and further, their generated EEG signals are generally chaotic in another sense, because, with respect to time, the amplitude changes continuously. A reliable and non-invasive measurement of memory load which will be made continuously while performing a cognitive task would be very helpful for assessing cognitive function, crucial for the prevention of decision-making errors, and also the development of adaptive user interfaces. Such a measurement could help to keep up the efficiency and productivity in task completion, work performance, and to avoid cognitive overload, especially in critical/high mental load workplaces like traffic control, military operations, and rescue commands. We have measured the linear and nonlinear dynamics of the EEG signals in subjects undergoing mental arithmetic task and measured the cognitive load on the brain continuously. We have also differentiated the subjects who can perform a mental task good and bad and developed a system using support vector machine to differentiate rest and task states.
Characteristics, outcome and predictors of in-hospital mortality in an elderly population from a SARS-CoV-2 outbreak in a long-term care facility
Authors: Trecarichi Enrico Maria , Mazzitelli Maria , Serapide Francesca , Pelle Maria Chiara , Tassone Bruno , Arrighi Eugenio , Perri Graziella , Fusco Paolo , Scaglione Vincenzo , Davoli Chiara , Lionello Rosaria , Gamba Valentina La , Marrazzo Giuseppina , Busceti Maria Teresa , Giudice Amerigo , Ricchio Marco , Cancelliere Anna , Lio Elena , Procopio Giada , Costanzo Francesco Saverio , Foti Daniela Patrizia , Matera Giovanni , Torti Carlo ,   IDTM UMG COVID-19 Group
Published: July 2020

Since December 2019, coronavirus disease 2019 (COVID-19) pandemic has spread from China all over the world, many COVID-19 outbreaks have been reported in long-term care facilities (LCTF). However, data on clinical characteristics and prognostic factors in such settings are scarce. We conducted a retrospective, observational cohort study to assess clinical characteristics and baseline predictors of mortality of COVID-19 patients hospitalized after an outbreak of SARS-CoV-2 infection in a LTCF.

A total of 50 patients were included. Mean age was 80 years (SD, 12 years), and 24/50 (57.1%) patients were males. A total of 42/50 (84%) patients experienced symptoms of SARS-CoV-2 infection. The overall in-hospital mortality rate was 32%. In Cox regression, significant predictors of in-hospital mortality were: hypernatremia (HR 9.12), lymphocyte count <1000 cells/µL (HR 7.45), cardiovascular diseases other than hypertension (HR 6.41), and higher levels of serum interleukin-6 (IL-6, pg/mL) (HR 1.005).

Our study shows a high in-hospital mortality rate in a cohort of elderly patients with COVID-19 and hypernatremia, lymphopenia, CVD other than hypertension, and higher IL-6 serum levels were identified as independent predictors of in-hospital mortality. Further studies are necessary to better understand and confirm our findings in the setting of a LTCF outbreak of COVID-19.
Low-Impact Social Distancing Interventions to Mitigate Local Epidemics of SARS-CoV-2
Authors: Jackson Michael L.
Published: July 2020

Background

After many jurisdictions have implemented intensive social distancing to suppress SARS-CoV-2 transmission, the challenge now is to mitigate the ongoing COVID-19 epidemic without overburdening economic and social activities. This report explores “low-impact” interventions to mitigate SARS-CoV-2 with a minimum of social and economic disruption.

Methods

An agent-based model simulated the population of King County, Washington, with agents that interact in homes, schools, workplaces, and other community sites. SARS-CoV-2 transmission probabilities were estimated by fitting simulated to observed hospital admissions from February – May 2020. Interventions considered were (a) encouraging telecommuting; (b) reducing contacts to seniors and nursing home residents; (c) modest reductions to contacts outside of the home; (d) encouraging self-isolation of persons with COVID-19 symptoms; (e) rapid testing and household quarantining.

Results

Individual interventions are not expected to have a large impact on COVID-19 hospitalizations. No intervention reduced COVID-19 hospitalizations by more than 12.7% (95% confidence interval [CI], 12.0% to 13.3%). Removing all interventions would result in nearly 42,000 COVID- 19 hospitalizations between June 2020 and January 2021, with peak hospital occupancy exceeding available beds 6-fold. Combining the interventions is predicted to reduce total hospitalizations by 48% (95% CI, 47-49%), with peak COVID-19 hospital occupancy of 70% of total beds. Targeted school closures can further reduce the peak occupancy.

Conclusions

Combining low-impact interventions may mitigate the course of the COVID-19 epidemic, keeping hospital burden within the capacity of the healthcare system. Under this approach SARS-CoV-2 can spread through the community, moving toward herd immunity, while minimizing social and economic disruption.