bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospital Length of Stay, Charges, and Costs Associated With a Diagnosis of Obesity in US Children and Youth, 2006–2016
Authors: Kompaniyets Lyudmyla , Lundeen Elizabeth A. , Belay Brook , Goodman Alyson B. , Tangka Florence , Blanck Heidi M.
Published: July 2020

Background:

Childhood obesity is linked with adverse health outcomes and associated costs. Current information on the relationship between childhood obesity and inpatient costs is limited.

Objective:

The objective of this study was to describe trends and quantify the link between childhood obesity diagnosis and hospitalization length of stay (LOS), costs, and charges.

Research Design:

We use the National Inpatient Sample data from 2006 to 2016.

Subjects:

The sample includes hospitalizations among children aged 2–19 years. The treatment group of interest includes child hospitalizations with an obesity diagnosis.

Measures:

Hospital LOS, charges, and costs associated with a diagnosis of obesity.

Results:

We find increases in obesity-coded hospitalizations and associated charges and costs during 2006–2016. Obesity as a primary diagnosis is associated with a shorter hospital LOS (by 1.8 d), but higher charges and costs (by $20,879 and $6049, respectively); obesity as a secondary diagnosis is associated with a longer LOS (by 0.8 d), and higher charges and costs of hospitalizations (by $3453 and $1359, respectively). The most common primary conditions occurring with a secondary diagnosis of obesity are pregnancy conditions, mood disorders, asthma, and diabetes; the effect of a secondary diagnosis of obesity on LOS, charges, and costs holds across these conditions.

Conclusions:

Childhood obesity diagnosis-related hospitalizations, charges, and costs increased substantially during 2006–2016, and obesity diagnosis is associated with higher hospitalization charges and costs. Our findings provide clinicians and policymakers with additional evidence of the economic burden of childhood obesity and further justify efforts to prevent and manage the disease.
Clinical expression of endocrine disruptors in children
Authors: Iughetti Lorenzo , Lucaccioni Laura , Street Maria E. , Bernasconi Sergio
Published: July 2020

Purpose of review

Health status is the result of complex interaction between individual factors, general environmental factors and specific factors as nutrition or the presence of chemicals. Aim of this review is to point out the more recent knowledge covering the role of the endocrine disrupting chemical (EDC) on pediatric population wellbeing.

Recent findings

Prenatal, postnatal life and puberty are the three main temporal windows of susceptibility when EDCs may act. The mechanism is independent from dose or duration of exposition, sex, age or combination of chemicals and may also be transgenerational, affecting both growth and pubertal timing. A window of susceptibility for breast cancer has been detected. Thyroid gland is influenced by environmental chemicals, bothin uteroand during childhood. Alteration in Thyrotropin stimulating hormone (TSH) levels and neurodevelopmental impairment have been demonstrate. It has been detected a pro-obesogenic action of specific chemicals, impairing also glucose homeostasis during childhood.

With a multidisciplinary approach and the use of big data platforms, an attempt has to be made to verify biological variations related to a disease, and how much the risk is influenced by the presence of the endocrine disruptors. This may help the future generation to better interpret uncommunicable diseases.
Pediatric kidney transplantation in the United States
Authors: Etesami Kambiz , Lestz Rachel , Hogen Rachel
Published: July 2020

Purpose of review

Pediatric kidney transplantation has made great strides over the preceding years. It has become an accepted and successful remedy for thousands of patients worldwide. For best outcomes, it must be viewed and treated as a distinct entity from adult transplantation with focus on the unique challenges particular to its cohort.

Recent findings

Although efforts have been made to decrease geographic disparity and increase allograft access throughout, an unintended consequence has been prolonged wait times for pediatric patients. Concurrently, ideally size-matched organs from older pediatric donors are also being bypassed. Nevertheless, advances in surgical technique and a better understanding of the limits of donor–recipient pairing have facilitated continued usage of adult kidneys for both infants and small for age children. Immunosuppression optimization has meant mean allograft survival measured in decades.

Enhanced access is needed to better size-matched organs for pediatric recipients, helping diminish wait times for the youngest patients, and improving their long-term prognosis. Longitudinal multicenter studies are needed to help standardize protocols, especially as it relates to optimal surgical and perioperative management. Advances in immunosuppression will continue to enhance patient and graft survival while minimizing adverse effects.
Developments in diagnosis and treatment of people with borderline personality disorder
Authors: Rao Sathya , Heidari Parvaneh , Broadbear Jillian H.
Published: July 2020

Purpose of review

Borderline personality disorder (BPD) attracts significant attention from clinicians and researchers alike. Despite increased recognition and willingness to diagnose BPD, most effective treatment approaches remain inaccessible to most. We consider recent developments in the diagnosis and treatment of BPD.

Recent findings

A literature search of EMBASE and PsychINFO, using the search terms ‘borderline personality disorder,’ ‘diagnosis’ and ‘treatment’ for publications since October 2018, yielded over 300 articles and reviews. The literature highlights the increasing awareness of the diagnostic complexity of BPD as well as the emerging significance of ‘common factors’ and stepped care approaches for managing and treating the disorder.

Clinical practice is evolving to embrace more holistic diagnostic approaches, generalist treatment frameworks and stepped-care models that can be tailored to fit individual needs and service resources. The new frontiers in this field include expansion of timely treatment options, improved knowledge regarding the expression and management of BPD in men, adolescents and the elderly, and bridging cultural divides to create a worldwide population approach.
Community mental healthcare: new developments and innovative strategies
Authors: Bajraktarov Stojan , Kalpak Gjorgji , Jovanovic Nikolina
Published: July 2020

Purpose of review

The aim of this scoping review was to identify and map the available evidence on recent innovations in community mental healthcare across the globe.

Recent findings

This review highlights the different innovative approaches and strategies being currently used in the field of community mental health. Key approaches found in the reviewed studies include collaborative care with the inclusion of peer workers, growing use of e-health and telepsychiatry, improved reforms on national mental health policies and de-institutionalization, modification of outreach models and mental health promotion in the community. The studies reviewed here suggest that continued innovation and implementation of new models and strategies have the potential to reduce the burden of disease and increase the quality of life for patients with mental health issues.

Growing body of evidence shows that integrative care is the new standard of care for people with mental illnesses, with necessity of continuity of care from emergency department to community mental health services. Social determinants of rehabilitation and recovery, and peers support remain a new main topic of research in area of treatment of people with severe mental illnesses. E-health tools are becoming prevalent in the processes of promotion, prevention and treatment in mental healthcare.
Acoustic allometry and vocal learning in mammals
Authors: Garcia Maxime , Ravignani Andrea
Published: July 2020

Acoustic allometryis the study of how animal vocalizations reflect their body size. A key aim of this research is to identify outliers to acoustic allometry principles and pinpoint the evolutionary origins of such outliers. A parallel strand of research investigates species capable ofvocal learning, the experience-driven ability to produce novel vocal signals through imitation or modification of existing vocalizations. Modification of vocalizations is a common feature found when studying both acoustic allometry and vocal learning. Yet, these two fields have only been investigated separately to date. Here, we review and connect acoustic allometry and vocal learning across mammalian clades, combining perspectives from bioacoustics, anatomy and evolutionary biology. Based on this, we hypothesize that, as a precursor to vocal learning, some species might have evolved the capacity for volitional vocal modulation via sexual selection for ‘dishonest' signalling. We provide preliminary support for our hypothesis by showing significant associations between allometric deviation and vocal learning in a dataset of 164 mammals. Our work offers a testable framework for future empirical research linking allometric principles with the evolution of vocal learning.
The nuclear envelope: LINCing tissue mechanics to genome regulation in cardiac and skeletal muscle
Authors: Piccus Rachel , Brayson Daniel
Published: July 2020

Regulation of the genome is viewed through the prism of gene expression, DNA replication and DNA repair as controlled through transcription, chromatin compartmentalisation and recruitment of repair factors by enzymes such as DNA polymerases, ligases, acetylases, methylases and cyclin-dependent kinases. However, recent advances in the field of muscle cell physiology have also shown a compelling role for ‘outside-in’ biophysical control of genomic material through mechanotransduction. The crucial hub that transduces these biophysical signals is called the Linker of Nucleoskeleton and Cytoskeleton (LINC). This complex is embedded across the nuclear envelope, which separates the nucleus from the cytoplasm. How the LINC complex operates to mechanically regulate the many functions of DNA is becoming increasingly clear, and recent advances have provided exciting insight into how this occurs in cells from mechanically activated tissues such as skeletal and cardiac muscle. Nevertheless, there are still some notable shortcomings in our understanding of these processes and resolving these will likely help us understand how muscle diseases manifest at the level of the genome.
A data-based mathematical modelling study to quantify the effects of ciprofloxacin and ampicillin on the within-host dynamics of
Salmonella enterica
during treatment and relapse
Authors: Vlazaki Myrto , Rossi Omar , Price David J. , McLean Callum , Grant Andrew J. , Mastroeni Pietro , Restif Olivier
Published: July 2020

Antibiotic therapy has drastically reduced the mortality and sequelae of bacterial infections. From naturally occurring to chemically synthesized, different classes of antibiotics have been successfully used without detailed knowledge of how they affect bacterial dynamics
in vivo
. However, a proportion of patients receiving antimicrobial therapy develop recrudescent infections post-treatment. Relapsing infections are attributable to incomplete clearance of bacterial populations following antibiotic administration; the metabolic profile of this antibiotic-recalcitrant bacterial subpopulation, the spatio-temporal context of its emergence and the variance of antibiotic–bacterial interactions
in vivo
remain unclear. Here, we develop and apply a mechanistic mathematical model to data from a study comparing the effects of ciprofloxacin and ampicillin on the within-host dynamics of
Salmonella enterica
serovar Typhimurium in murine infections. Using the inferential capacity of our model, we show that the antibiotic-recalcitrant bacteria following ampicillin, but not ciprofloxacin, treatment belong to a non-replicating phenotype. Aligning with previous studies, we independently estimate that the lymphoid tissues and spleen are important reservoirs of non-replicating bacteria. Finally, we predict that post-treatment, the progenitors of the non-growing and growing bacterial populations replicate and die at different rates. Ultimately, the liver, spleen and mesenteric lymph nodes are all repopulated by progenitors of the previously non-growing phenotype in ampicillin-treated mice.
Pelagihabitans pacificus gen. nov., sp. nov., a member of the family Flavobacteriaceae isolated from a deep-sea seamount
Authors: Wang Qian , Liu Feng , Zhang De-Chao
Published: July 2020

The Gram-stain-negative, orange-pigmented, non-spore-forming, non-motile, strictly aerobic, rod-shaped bacterial strain, designated TP-CH-4T, was isolated from a seamount near the Yap Trench in the tropical western Pacific. The optimal growth conditions were determined to be at pH 7–8, 25–30 °C and in the presence of 2 % (w/v) NaCl. The major respiratory quinone was MK-6. The polar lipid profile contained phosphatidylethanolamine, two unidentified aminolipids, two unidentified phospholipids and three unidentified polar lipids. The predominant cellular fatty acids were iso-C15 : 0 and summed feature 1 (composed of C13 : 03-OH and/or iso-C15 : 1H). Phylogenetic analysis of 16S rRNA gene sequences revealed that strain TP-CH-4T was a member of the family

Flavobacteriaceae

and formed a distinct lineage. Strain TP-CH-4T displayed highest sequence similarities to

Pseudozobellia thermophila

KMM 3531T (95.1 %) and

Flagellimonas flava

A11T (93.9 %). Genome sequencing revealed the strain TP-CH-4T has a genome size of 4.5 Mbp and a G+C content of 44.5 mol%. Collectively, based on phenotypic, chemotaxonomic, phylogenetic and genomic evidence, strain TP-CH-4T represents a novel species of a novel genus of the family

Flavobacteriaceae

, for which the name Pelagihabitans pacificus gen. nov., sp. nov. is proposed. The type strain of Pelagihabitans pacificus is TP-CH-4T (=CGMCC 1.17120T=KCTC 72434T).
The socio-economic determinants of COVID-19: A spatial analysis of German county level data
Authors: Ehlert Andree
Published: July 2020

The study explores the influence of socio-economic variables on case and death rates of the COVID-19 pandemic in Germany until mid-June 2020. It covers Germany’s 401 counties by multivariate spatial models that can take into account regional interrelationships and possible spillover effects. The case and death rates are, for example, significantly positively associated with early cases from the beginning of the epidemic, the average age, the population density and the number of people employed in elderly care. By contrast, they are significantly negatively associated with the density of schoolchildren and infant care as well as the density of doctors. In addition, for certain variables significant spillover effects on the case numbers of neighbouring regions could be identified, which have a different sign than the overall effects and thus give cause for further analyses of the mechanisms of action of COVID-19 infections. The results complement the knowledge about COVID-19 infection beyond the clinical risk factors discussed so far by a socio-economic perspective. The findings can contribute to the targeted derivation of political measures and their review, as is currently being discussed in particular for the tourism and education sectors.
Triplex Real Time RT-PCR for N1, N2 and RP probes from CDC EUA SARS-CoV-2 diagnosis kit
Authors: Freire-Paspuel Byron , Vega-Mariño Patricio , Velez Alberto , Cruz Marilyn , Garcia-Bereguiain Miguel Angel
Published: July 2020

CDC protocol for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include 3 targets for detection (N1, N2 and RP) labelled with FAM so 3 PCR reactions are required per sample. We developed a triplex, real-time reverse transcription PCR for SARS-CoV-2 that maintained clinical performance compared with CDC singleplex assay. This protocol could speed up detection and save reagents during current SARS-CoV-2 testing supplies shortage.
FreeClimber: Automated quantification of climbing performance inDrosophila, with examples from mitonuclear genotypes
Authors: Spierer Adam N. , Yoon Denise , Zhu Chen-Tseh , Rand David M.
Published: July 2020

Negative geotaxis (climbing) performance is a useful metric for quantifyingDrosophilahealth and vigor. Manual methods to quantify climbing performance are slow, tedious, and may be systematically biased, while available computational methods have inflexible hardware or software requirements. We present an alternative: FreeClimber. This open source, Python-based pipeline subtracts a video’s static background to improve spot detection for moving flies in heterogeneous backgrounds. FreeClimber calculates a cohort’s velocity as the slope of the most linear portion of a mean-vertical position vs. time plot. It can run from a graphical user interface for parameter optimization or a command line interface for high-throughput and automated batch processing. It outputs calculated slopes, spot locations for follow up analyses such as tracking, and several visualizations and diagnostic plots. We demonstrate FreeClimber’s utility in a longitudinal study for endurance exercise performance inDrosophilausing six distinct mitochondrial haplotypes paired with a commonw1118nuclear background.

Summary statement

FreeClimber quantifies the climbing velocity for a group of flies, eliminating systematic biases associated with traditional manual methods in a high throughput and automated (graphical and/or command line-based) platform.
Chloroquine and Hydroxychloroquine for the treatment of COVID-19: A Systematic Review and Meta-analysis
Authors: Elavarasi Arunmozhimaran , Prasad Manya , Seth Tulika , Sahoo Ranjit Kumar , Madan Karan , Nischal Neeraj , Soneja Manish , Sharma Atul , Maulik Subir Kumar , Shalimar  , Garg Pramod
Published: July 2020

Background

There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain.

Objective

We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19.

Methods

Two reviewers searched for published and pre-published relevant articles between December 2019 to 8th June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa scale. The quality of evidence was graded as per the GRADE approach.

Results

We reviewed 12 observational and 3 randomized trials which included 10659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46], time to fever resolution [mean difference −0.54 days (-1.19-011)] or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes.

Author’s Conclusion

The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19..
Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea
Authors: An Min Ho , Kim Min Seo , Park Yu-Kyung , Kim Bong-Ok , Kang Seok Ho , Kim Won Jun , Park Sung Kyu , Park Hea-Woon , Yang Wonjong , Jang Joonyoung , Jang Soon-Woo , Hwang Tae-Ho
Published: July 2020

Objectives

To assess the efficacy of hydroxychloroquine on mild-moderate COVID-19 patients in South Korea.

Methods

A retrospective cohort study of the 358 laboratory-confirmed SARS-CoV-2 (COVID-19) patients was conducted. 226 patients met inclusion criteria for analysis. Propensity score matching (PSM) and Cox regression method were utilized to control and adjust for confounding factors. Mild to moderate COVID-19 patients were managed with hydroxychloroquine (HQ) plus antibiotics (n = 31) or conservative treatment (n = 195).

Results

Kaplan-Meier curves drawn using propensity score-matched data revealed no differences between the length of time to viral clearance and duration of hospital stay between the two treatment arms (p=0.18, p=0.088). Multivariable Cox regression analysis similarly showed that time to viral clearance(Hazard ratio (HR) 0.97, [95%-confidence interval (CI): 0.57-1.67]) and symptom duration(HR 1.05, [95%-CI: 0.62-1.78]) were not different between groups. No severe adverse event or death was observed in either group.

Conclusions

HQ with antibiotics was not associated with better clinical outcomes in terms of time to viral clearance, length of hospital stay, and duration of symptoms compared to conservative treatment alone. Large prospective randomized trials are necessary for definitive conclusions.
PaintSHOP enables the interactive design of transcriptome- and genome-scale oligonucleotide FISH experiments
Authors: Hershberg Elliot A. , Close Jennie L. , Camplisson Conor K. , Attar Sahar , Chern Ryan , Liu Yuzhen , Akilesh Shreeram , Nicovich Philip R. , Beliveau Brian J.
Published: July 2020

Fluorescentin situhybridization (FISH) allows researchers to visualize the spatial position and quantity of nucleic acids in fixed samples. Recently, considerable progress has been made in developing oligonucleotide (oligo)-based FISH methods. These methods have enabled researchers to study the three-dimensional organization of the genome at super-resolution and visualize the spatial patterns of gene expression for thousands of genes in individual cells. While considerable progress has been made in developing new molecular methods that harness complex oligo libraries for FISH, there are few existing computational tools to support the bioinformatics workflows necessary to carry out these experiments. Here, we introduce Paint Server and Homology Optimization Pipeline (PaintSHOP), an interactive platform for the reproducible design of oligo FISH experiments. PaintSHOP enables researchers to identify probes for their experimental targets efficiently, to incorporate additional necessary sequences such as primer pairs, and to easily generate standardized files documenting the design of their libraries. Our platform integrates a machine learning model that quantitatively predicts probe specificity on the genome scale into a dynamic web application that creates ready-to-order probe sets for a wide variety of applications. The goal of this freely available web resource is to democratize and standardize the process of designing complex probe sets for the oligo FISH community. PaintSHOP can be accessed at:paintshop.io
Initial characterisation of commercially available ELISA tests and the immune response of the clinically correlated SARS-CoV-2 biobank “SERO-BL-COVID-19” collected during the pandemic onset in Switzerland
Authors: Kaltenbach Hans-Michael , Rudolf Fabian , Linnik Janina , Deichmann Julia , Ruf Therese , Altamura Raffaele , Kapetanovic Edo , Mason Derek , Wagner Bastian , Goetz Thomas , Mundorff Lukas , Stoll-Rudin Karin , Krebs Christina , Renz Tanja , Hochueli Thomas , Haymoz Sergio , Hosch Markus , Périat Nadine , Richert Michèle , Sesia Sergio , Paris Daniel , Quinto Carlos Beat , Probst-Hensch Nicole M. , Niederhauser Christoph , Reddy Sai , Nickel Beatrice , Savic Miodrag
Published: July 2020

Background

To accurately measure seroprevalance in the population, both the expected immune response as well as the assay performances have to be well characterised. Here, we describe the collection and initial characterisation of a blood and saliva biobank obtained after the initial peak of the SARS-CoV-2 pandemic in Switzerland.

Methods

Two laboratory ELISAs measuring IgA & IgG (Euroimmun), and IgM & IgG (Epitope Diagnostics) were used to characterise the biobank collected from 349 re- and convalescent patients from the canton of Basel-Landschaft.

Findings

The antibody response in terms of recognized epitopes is diverse, especially in oligosymptomatic patients, while the average strength of the antibody response of the population does correlate with the severity of the disease at each time point.

Interpretation

The diverse immune response presents a challenge when conducting epidemiological studies as the used assays only detect∼90% of the oligosymptomatic cases. This problem cannot be rectified by using more sensitive assay setting as they concomitantly reduce specificity.

Funding

Funding was obtained from the “Amt für Gesundheit” of the canton Basel-Landschaft, Switzerland.
The mental health impact of COVID-19 and pandemic related stressors among adults in the UK
Authors: Chandola Tarani , Kumari Meena , Booker Cara L , Benzeval Michaela J
Published: July 2020

Background

The coronavirus pandemic has resulted in a wide range of social and economic changes that could, in turn, have affected the mental health of the UK adult population. Previous research has not been able to measure the broad range of potential stressors, nor examine whether recent changes in those stressors have positively or negatively impacted on common mental disorders. Furthermore, it is unclear whether the stressful impact of the lockdown on mental health has accumulated over time or whether people have adapted to the new conditions of lockdown. This study examines whether there was an increase in the prevalence and incidence of Common Mental Disorders (CMD) in the UK adult population during the first few months of lockdown related to the coronavirus pandemic and whether changes in CMD were associated with an increase in stressors related to lockdown and the pandemic.

Methods

Longitudinal data from the UK Household Longitudinal Study (wave 9: 2017-2019 and waves 1 and 2 of the Coronavirus survey in April and May 2020 respectively), a representative sample of UK population, were analysed. Common mental disorders (CMD) were measured using the GHQ-12 (cut off >2) at all waves. The difference in the GHQ-12 (using Likert scores) between waves measured changes in psychological well-being. The incidence of CMD and changes in psychological well-being were analysed in relation to pandemic specific stressors and changes in economic, financial, household and psychosocial stressors.

Findings

Around 30% of UKHLS adults without CMD in 2017/9 had a CMD in April 2020. However from April to May 2020, the incidence reduced considerably to below 13%. Much of the increase in incident CMD between April and May was associated with an increase in feelings of loneliness, but some of this increase was also associated with increasing domestic work demands (arising out of childcare and home-schooling), working from home, and the receipt of care from outside the home. The reduction in the incidence of many of these stressors in May (compared to April) coincided with a reduction in the incidence of CMD in May.

Conclusion

The pandemic and resultant lockdown were associated with an increase in the incidence of CMD in the UK adult population initially in April 2020. These changes were associated with increases in feelings of loneliness and stressors related to work and domestic life and receipt of care. There was some evidence of adaptation to many of these stressors over the lockdown period by May 2020. However, if levels of unemployment and redundancy increase in the near future, the implications for the mental health of the population need careful thought and monitoring.
A topic analysis of traditional and social media news coverage of the early COVID-19 pandemic and implications for public health communication
Authors: Chipidza Wallace , Akbaripourdibazar Elmira , Gwanzura Tendai , Gatto Nicole M.
Published: July 2020

Knowledge gaps may initially exist among scientists, medical and public health professionals during pandemics, which are fertile grounds for misinformation in news media. We characterized and compared COVID-19 coverage in newspapers, television, and social media, and discussed implications for public health communication strategies that are relevant to an initial pandemic response. We conducted a Latent Dirichlet Allocation (LDA), an unsupervised topic modelling technique, analysis of 3,271 newspaper articles, 40 cable news shows transcripts, 96,000 Twitter posts, and 1,000 Reddit posts during March 4 - 12, 2020, a period chronologically early in the timeframe of the COVID-19 pandemic. Coverage of COVID-19 clustered on topics such as epidemic, politics, and the economy, and these varied across media sources. Topics dominating news were not predominantly health-related, suggesting a limited presence of public health in news coverage in traditional and social media. Examples of misinformation were identified particularly in social media. Public health entities should utilize communication specialists to create engaging informational content to be shared on social media sites. Public health officials should be attuned to their target audience to anticipate and prevent spread of common myths likely to exist within a population. This will help control misinformation in early stages of pandemics.
Two-Stage Adaptive Pooling with RT-qPCR for COVID-19 Screening
Authors: Heidarzadeh Anoosheh , Narayanan Krishna
Published: July 2020

We propose two-stage adaptive pooling schemes, 2-STAP and 2-STAMP, for detecting COVID-19 using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) test kits. Similar to the Tapestry scheme of Ghoshet al., the proposed schemes leverage soft information from the RT-qPCR process about the total viral load in the pool. This is in contrast to conventional group testing schemes where the measurements are Boolean. The proposed schemes provide higher testing throughput than the popularly used Dorfman’s scheme. They also provide higher testing throughput, sensitivity and specificity than the state-of-the-art non-adaptive Tapestry scheme. The number of pipetting operations is lower than state-of-the-art non-adaptive pooling schemes, and is higher than that for the Dorfman’s scheme. The proposed schemes can work with substantially smaller group sizes than non-adaptive schemes and are simple to describe. Monte-Carlo simulations using the statistical model in the work of Ghoshet al. (Tapestry) show that 10 infected people in a population of size 961 can be identified with 70.86 tests on the average with a sensitivity of 99.50% and specificity of 99.62%. This is 13.5x, 4.24x, and 1.3x the testing throughput of individual testing, Dorfman’s testing, and the Tapestry scheme, respectively.
TLR7 ligation augments haematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signalling and enhanced differentiation
Authors: Peña Oscar A , Lubin Alexandra , Rowell Jasmine , Hockings Catherine , Jung Youngrock , Hoade Yvette , Dace Phoebe , Valdivia Leonardo E , Tuschl Karin , Boiers Charlotta , Virgilio Maria C , Richardson Simon , Payne Elspeth M
Published: July 2020

Myelodysplastic syndrome (MDS) is a haematological malignancy characterised by blood cytopenias and predisposition to acute myeloid leukaemia (AML). Therapies for MDS are lacking, particularly those that impact the early stages of disease. We developed a model of MDS using zebrafish using knockout of Rps14, the primary mediator of the anaemia associated with del (5q) MDS. These mutant animals display dose- and age-dependent abnormalities in haematopoiesis, culminating in bone marrow failure with dysplastic features. We utilized rps14 knockdown to undertake anin vivosmall molecule screen to identify compounds that ameliorate the MDS phenotype, identifying imiquimod, an agonist of TLR7 and TLR8. Imiquimod alleviates anaemia by promoting haematopoietic stem and progenitor cell expansion and erythroid differentiation, the mechanism of which is dependent on TLR7 ligation. TLR7 activation in this setting paradoxically promoted an anti-inflammatory gene signature suggesting crosstalk between pro-inflammatory pathways endogenous to Rps14 loss and TLR7 pathway activation. Finally, we show that in highly purified human bone marrow samples from anaemic patients, imiquimod leads to an increase in erythroid output from myelo-erythroid progenitors and common myeloid progenitors. Our findings have both specific implications for the development of targeted therapeutics for del (5q) MDS and wider significance identifying a potential role for TLR7 ligation in modifying anaemia.
MDA5 is an essential vita-PAMP sensor necessary for host resistance againstAspergillus fumigatus
Authors: Wang Xi , Caffrey-Carr Alayna K. , Liu Ko-wei , Espinosa Vanessa , Croteau Walburga , Dhingra Sourabh , Rivera Amariliz , Cramer Robert A. , Obar Joshua J.
Published: July 2020

RIG-I like receptors (RLR) are cytosolic RNA sensors that signal through the MAVS adaptor to activate interferon responses against viruses. Whether the RLR family has broader effects on host immunity against other pathogen families remains to be fully explored. Herein we demonstrate that MDA5/MAVS signaling was essential for host resistance against pulmonaryAspergillus fumigatuschallenge through the regulation of antifungal leukocyte responses in mice. Activation of MDA5/MAVS signaling was driven by dsRNA from liveA. fumigatusserving as a key vitality-sensing pattern-recognition receptor. Interestingly, induction of type I interferons afterA. fumigatuschallenge was only partially dependent on MDA5/MAVS signaling, whereas type III interferon expression was entirely dependent on MDA5/MAVS signaling. Ultimately, type I and III interferon signaling drove the expression of CXCL10. Furthermore, the MDA5/MAVS-dependent interferon response was critical for the induction of optimal antifungal neutrophil killing ofA. fumigatusspores. In conclusion, our data broaden the role of the RLR family to include a role in regulating antifungal immunity againstA. fumigatus.

KEY POINTS

MDA5 is essential for maintaining host resistance against Aspergillus fumigatus

MDA5 serves as a critical vitality sensor after fungal challenge

MDA5 is essential for IFNλ expression and anti-fungal neutrophil killing
Gene Expression Network Analysis Provides Potential Targets Against SARS-CoV-2
Authors: Hernández Cordero Ana I. , Li Xuan , Yang Chen Xi , Milne Stephen , Bossé Yohan , Joubert Philippe , Timens Wim , van den Berge Maarten , Nickle David , Hao Ke , Sin Don D.
Published: July 2020

BACKGROUND

Cell entry of SARS-CoV-2, the novel coronavirus causing COVID-19, is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We aimed to identify and characterize genes that are co-expressed withACE2andTMPRSS2, and to further explore their biological functions and potential as druggable targets.

METHODS

Using the gene expression profiles of 1,038 lung tissue samples, we performed a weighted gene correlation network analysis (WGCNA) to identify modules of co-expressed genes. We explored the biology of co-expressed genes using bioinformatics databases, and identified known drug-gene interactions.

RESULTS

ACE2was in a module of 681 co-expressed genes; 12 genes with moderate-high correlation withACE2(r>0.3, FDR<0.05) had known interactions with existing drug compounds.TMPRSS2was in a module of 1,086 co-expressed genes; 15 of these genes were enriched in the gene ontology biologic process ‘Entry into host cell’, and 53TMPRSS2-correlated genes had known interactions with drug compounds.

CONCLUSION

Dozens of genes are co-expressed withACE2andTMPRSS2, many of which have plausible links to COVID-19 pathophysiology. Many of the co-expressed genes are potentially targetable with existing drugs, which may help to fast-track the development of COVID-19 therapeutics.
Structural and molecular basis of cross-seeding barriers in amyloids
Authors: Daskalov A. , Martinez D. , Coustou V. , El Mammeri N. , Berbon M. , Andreas L.B. , Bardiaux B. , Stanek J. , Noubhani A. , Kauffmann B. , Wall J.S. , Pintacuda G. , Saupe S.J. , Habenstein B. , Loquet A.
Published: July 2020

Neurodegenerative disorders are frequently associated with β-sheet-rich amyloid deposits. Amyloid-forming proteins can aggregate under different structural conformations known as strains, which can exhibit a prion-like behaviour and distinct patho-phenotypes. Precise molecular determinants defining strain specificity and cross-strain interactions (cross-seeding) are currently unknown. The HET-s prion protein from the fungusPodospora anserinarepresents a model system to study the fundamental properties of prion amyloids. Here, we report the amyloid prion structure of HELLF, a distant homolog of the model prion HET-s. We find that these two amyloids, sharing only 17% sequence identity, have nearly identical β-solenoid folds but lack cross-seeding abilityin vivo, indicating that prion specificity can differ in extremely similar amyloid folds. We engineer the HELLF sequence to explore the limits of the sequence-to-fold conservation and to pinpoint determinants of cross-seeding and prion specificity. We find that amyloid fold conservation occurs even at an exceedingly low level of identity to HET-s (5%). Next, we derive a HELLF-based sequence, termed HEC, able to breach the cross-seeding barrierin vivobetween HELLF and HET-s, unveiling determinants controlling cross-seeding at residue level. These findings show that virtually identical amyloid backbone structures might not be sufficient for cross-seeding and that critical side-chain positions could determine the seeding specificity of an amyloid fold. Our work redefines the conceptual boundaries of prion strain and shed new light on key molecular features concerning an important class of pathogenic agents.
Bifurcation and sensitivity analysis reveal key drivers of multistability in a model of macrophage polarization
Authors: Josefine Frank Anna-Simone , Larripa Kamila , Ryu Hwayeon , Snodgrass Ryan , Röblitz Susanna
Published: July 2020

In this paper, we present and analyze a mathematical model for polarization of a single macrophage which, despite its simplicity, exhibits complex dynamics in terms of multistability. In particular, we demonstrate that an asymmetry in the regulatory mechanisms and parameter values is important for observing multiple phenotypes. Bifurcation and sensitivity analyses show that external signaling cues are necessary for macrophage commitment and emergence to a phenotype, but that the intrinsic macrophage metabolism is equally important. Based on our numerical results, we formulate hypotheses that could be further investigated byin vitroexperiments to deepen our understanding of macrophage polarization.

2010 MSC

93A30, 34C23, 49Q12, 92C42, 37N25
Prime editing efficiently generates W542L and S621I double mutations in two ALS genes in maize
Authors: Jiang Yuan-Yuan , Chai Yi-Ping , Lu Min-Hui , Han Xiu-Li , Lin Qiupeng , Zhang Yu , Zhang Qiang , Zhou Yun , Wang Xue-Chen , Gao Caixia , Chen Qi-Jun
Published: July 2020

A novel and universal CRISPR/Cas-derived precision genome-editing technology named prime editing was developed. However, low efficiency of prime editing was shown in transgenic rice lines. We reasoned that enhancing pegRNA expression would improve prime-editing efficiency. In this report, we describe two strategies for enhancing pegRNA expression. We constructed a prime-editing vector harboring two pegRNA variants for W542L and S621I double mutations inZmALS1andZmALS2. Compared with previous reports in rice, we achieved much higher prime-editing efficiency in maize. Our results are inspiring and provide a direction for the optimization of plant prime editors.
Deletion ofTrpm4alters the function and expression of NaV1.5 channel in murine cardiac myocytes
Authors: Cherian Ozhathil Lijo , Rougier Jean-Sébastien , Arullampalam Prakash , Essers Maria C. , Abriel Hugues
Published: July 2020

Transient receptor potential melastatin member 4 (TRPM4) encodes a Ca+-activated non-selective cation channel that is functionally expressed in several tissues including the heart. Pathogenic mutants inTRPM4have been reported in patients with inherited cardiac diseases including conduction block and Brugada syndrome. Heterologous expression of mutant channels in cell lines indicates that these mutations can lead to an increase or decrease in TRPM4 expression and function at the cell surface. While the expression and clinical variant studies further stress the importance of TRPM4 in cardiac function, the cardiac electrophysiological phenotypes inTrpm4knockdown mouse models remain incompletely characterized. To study the functional consequences ofTrpm4deletion on cardiac electrical activity in mice, we performed perforated-patch clamp and immunohistochemistry studies on isolated atrial and ventricular cardiac myocytes and surface, pseudo and intracardiac ECGs eitherin vivoor on Langendorff-perfused explanted mouse hearts. We observed that Trpm4 is expressed in atrial and ventricular cardiac myocytes and that deletion ofTrpm4unexpectedly reduces the peak Na+currents in the myocytes. Hearts fromTrpm4-/-mice presented increased sensitivity towards mexiletine, a Na+channel blocker, and slower intraventricular conduction, consistent with the reduction of peak Na+current observed in the isolated cardiac myocytes. This reduction in Na+current is explained by the observed decrease in protein expression of NaV1.5 inTrpm4-/-mice. This study suggests that Trpm4 expression impacts Na+current in murine cardiac myocytes and points towards a novel function of Trpm4 regulating the NaV1.5 expression in murine cardiac myocytes.
pH-dependent spontaneous hydrolysis rather than gut bacterial metabolism reduces levels of the ADHD treatment, Methylphenidate
Authors: Aresti-Sanz Julia , Maho Walid , Pereira Rob Rodrigues , Permentier Hjalmar , Aidy Sahar El
Published: July 2020

Methylphenidate is absorbed in the small intestine. The drug is known to have low bioavailability and a high interindividual variability in terms of response to the treatment. Gut microbiota has been shown to reduce the bioavailability of a wide variety of orally administered drugs. Here, we tested the ability of small intestinal bacteria to metabolize methylphenidate.In silicoanalysis identified several small intestinal bacteria to harbor homologues of the human carboxylesterase 1 enzyme responsible for the hydrolysis of methylphenidate in the liver. Despite our initial results hinting towards possible bacterial hydrolysis of the drug, up to 60% of methylphenidate was spontaneously hydrolyzed in the absence of bacteria and this hydrolysis was pH-dependent. Overall, the study shows that pH-dependent spontaneous hydrolysis rather than gut bacterial metabolism reduces levels of methylphenidate and suggest a role of the luminal pH in the bioavailability of the drug.
Genome-wide analysis of the polyamine oxidase gene family in wheat (Triticum aestivumL.) reveals involvement in temperature stress response
Authors: Gholizadeh Fatemeh , Mirzaghaderi Ghader
Published: July 2020

Amine oxidases (AOs) including copper containing amine oxidases (CuAOs) and FAD-dependent polyamine oxidases (PAOs) are associated with polyamine catabolism in the peroxisome, apoplast and cytoplasm and play an essential role in growth and developmental processes and response to biotic and abiotic stresses. Here, we identifiedPAOgenes in common wheat (Triticum aestivum),T. urartuandAegilops tauschiiand reported the genome organization, evolutionary features and expression profiles of the wheat PAO genes (TaPAO). Expression analysis using publicly available RNASeq data showed thatTaPAOgenes are expressed redundantly in various tissues and developmental stages. A large percentage ofTaPAOsrespond significantly to abiotic stresses, especially temperature (i.e. heat and cold stress). SomeTaPAOswere also involved in response to other stresses such as powdery mildew, stripe rust andFusariuminfection. Overall,TaPAOsmay have various functions in stress tolerances responses, and play vital roles in different tissues and developmental stages. Our results provided a reference for further functional investigation of TaPAO proteins.
Effects of exogenous β-glucanase on ileal digesta soluble β-glucan molecular weight, digestive tract characteristics, and performance of coccidiosis challenged broiler chickens fed hulless barley-based diets with and without medication
Authors: Karunaratne Namalika D. , Newkirk Rex W. , Ames Nancy P. , Van Kessel Andrew. G. , Bedford Michael R. , Classen Henry L.
Published: July 2020

Limited use of medication in poultry feed led to the investigation of exogenous enzymes as antibiotic alternatives for controlling enteric disease. The objective of this study was to evaluate the effects of diet β-glucanase (BGase) and medication on β-glucan depolymerization, digestive tract characteristics, and performance of broilers. Broilers were fed hulless barley (HB) based diets with BGase (Econase GT 200P from AB Vista; 0 and 0.1%) and medication (Bacitracin and Salinomycin Na; with and without) arranged as a 2 × 2 factorial. In Experiment 1, 160 broilers were housed in cages from d 0 to 28. Each treatment was assigned to 10 cages. In Experiment 2, broilers (2376) were housed in floor pens and challenged with a coccidiosis vaccine on d 5. Each treatment was assigned to one floor pen in each of nine rooms. In Experiment 1, the soluble β-glucan weight average molecular weight (Mw) in the ileal digesta was lower with medication in the 0% BGase treatments. Peak molecular weight (Mp) and Mw were lower with BGase regardless of medication. The maximum molecular weight for the smallest 10% β-glucan (MW-10%) was lower with BGase. In Experiment 2, Mp was lower with medication in 0% BGase treatments. Beta-glucanase resulted in lower Mp regardless of medication, and the degree of response was lower with medication. The MW-10% was lower with BGase despite antibiotic addition. Body weight gain (BWG) and feed efficiency were higher with medication regardless of BGase use through-out the trial (except d 11-22 feed efficiency). Beta-glucanase resulted in higher BWG after d 11, and lower and higher feed efficiency before and after d 11, respectively, in unmedicated treatments. In conclusion, BGase and medication caused the depolymerization of soluble ileal β-glucan. Beta-glucanase appeared as a partial replacement for diet medication to increase coccidiosis challenged broiler performance.