bluuebunny/crossref_metadata_2025 huggingface dataset:
HMGB1‐TLR4 in The Brainstem Nuclei Mediates Fructose‐induced Metabolic Syndrome
Authors: Ho Chiu-Yi , Chen Hsin-Hung , Cheng Pei-Wen , Lin Yu-Te , Tseng Chin-Jiuun
Published: April 2020

The metabolic syndrome caused by excessive consumption of fructose is one of a variety of abnormal physiological phenomena, which is related to cardiovascular diseases. Our previous study reported that hypertension and central insulin resistance in WKY rats were caused by fructose intake. Several studies have been reported that the intake of fructose causes central inflammation. Toll‐like receptor 4 (TLR4) play a key role of innate immune signaling and has been implicated in fructose‐induced metabolic syndrome rats. We analyzed systolic blood pressure, biochemical parameter, and TLR4‐signaling pathway of WKY rats and fructose‐intake rats treated with vehicle or CLI‐095 (12 mg×d−1 for 14 days through osmotic mini‐pump). We found that the systolic blood pressure of rats treated CLI‐095 was improved to the normotensive group. The body weight change was recovered to the rats treated with the vehicle. Serum glucose treated with CLI‐095 was restored and stabilized compared with the fructose group. Immunoblotting results showed HMGB1 and TLR4 rather than TLR2, TLR7, TLR9 were induced in the brainstem nuclei area. MyD88, phosphorylated TGF beta‐activated kinase 1 (TAK1) and JNK were inhibited in the CLI‐095 group. Neuroinflammatory indicator iNOS was reduced in the therapy group. These data demonstrated that TLR4 in the central brain participates in the regulation of blood pressure, glucose, and body weight, which suggested HMGB1‐TLR4 might be a potential target for therapeutic interventions in the condition with metabolic syndrome combined with neuroinflammation.

Support or Funding Information

This work was supported by the Ministry of Science and Technology grants 107‐2320‐B‐075B‐001 (to P.W.C.) and 107‐2320‐B‐075B‐002‐MY2 (to C.J.T.) and Kaohsiung Veterans General Hospital grants VGHKS108‐162 (to Y.T.L.) and VGHUST108‐G3‐1‐3 (to Y.T.L.).
Role of Stromal Interaction Molecule 1 in Arteriogenesis
Authors: Frost Michaela , Belmadani Souad , Matrougui Khalid
Published: April 2020

Introduction

Arteriogenesis is a vital process for maintaining blood supply in the event of abrupt obstruction of perfusion such as cardiac ischemia. Here, we sought to determine whether stromal‐interaction molecule 1 (STIM1) is a key molecular mechanism involved in arteriogenesis.

Hypothesis

We previously reported that disrupting STIM1 in vascular smooth muscle cells (VSMC’s) protects the heart against chronic ischemia; likely through the induction of arteriogenesis. We hypothesize that disrupting STIM1 specifically in VSMC’s results in greater cellular proliferation and migration, which subsequently aids in arteriogenesis.

Methods

We isolated VSMC’s from mice with a genetic knockdown of STIM1 (VSMCStim1−/−) and also from wild‐type mice (VSMCStim1+/+). We cultured these VSMC’s in vitro and measured well‐known anti‐angiogenic factors including; thrombospondin‐1 (TSP‐1), hydrogen peroxide‐inducible clone 5 (Hic‐5), and extracellular signal‐regulated kinase (ERK 1/2). Additionally, we assessed the levels of pro‐angiogenic agent, AMP‐activated protein kinase (AMPK). Lastly, we assessed VSMC proliferation and migration after scratch‐assay injury.

Results

Under basal conditions, Western blot analysis revealed that anti‐arteriogenic TSP‐1, Hic‐5, and phosphorylated ERK1/2 expressions were significantly decreased in VSMCStim1−/− when compared to VSMCStim1+/+. Western blotting also revealed that pro‐arteriogenic AMPK expression was increased in VSMCStim1−/− relative to VSMCStim1+/+. Moreover, using real time PCR, we found that TSP‐1 mRNA levels were significantly reduced in VSMCStim1−/− versus VSMCStim1+/+. Finally, the scratch‐assay injury revealed that VSMCStim1−/− migrate more efficiently than VSMCStim1+/+.

Conclusion

Our data illustrated that disrupting STIM1 in VSMC’s attenuates arteriogenic antagonists and enhances pro‐arteriogenic factors indicating that STIM1 as an important mechanism in arteriogenesis. Therefore, lowering STIM1 expression specifically in VSMC’s could be a potential therapy for conditions such ischemic heart diseases.

Support or Funding Information

AHA‐34380220
Skeletal muscle‐specific PFKFB3 expression rescues ischemic myopathy by enhancing glycolytic flux
Authors: Salyers Zachary R. , Thome Trace , Le Dennis , Coleman Madeline , Ryan Terence E.
Published: April 2020

INTRODUCTION

Peripheral artery disease (PAD) is caused by atherosclerotic occlusion in the lower extremities which leads to a spectrum of life‐altering symptomatology including claudication, ischemic rest pain, and gangrene requiring limb amputation.
Current treatment approaches for PAD are focused solely
on re‐establishing blood flow to the ischemic tissue, implying that blood flow is the decisive factor that determines whether or not the tissue survives. Unfortunately, clinical trials aimed to enhance angiogenesis have failed, suggesting the need to consider therapies that might also benefit other tissues in the ischemic limb, such as skeletal muscle. Under conditions of low oxygen cells must efficiently switch to non‐aerobic metabolism in order to maintain a cellular energy charge, which if dissipated with initiate necrotic cell death. The objective of this study was to determine if muscle‐specific overexpression of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase 3 (PFKFB3), an activator of glycolysis, could ameliorate ischemic myopathy in mice subjected to hindlimb ischemia.

METHODS AND RESULTS

Twelve‐week old male and female BALB/cJ mice (N=36) received intramuscular injections (5×1011 vg) of AAV9 encoding the PFKFB3 transgene or a GFP control driven by a skeletal muscle‐specific gene promoter (human skeletal actin, HSA). AAV‐expression was verified using immunofluorescence imaging, mRNA, and protein analysis. Three weeks following AAV injection, mice underwent unilateral hindlimb ischemia by ligation and excision of femoral artery. A sham surgery group underwent identical surgical procedure without ligation/excision. Mice were monitored for 28 days post‐surgery. Laser Doppler perfusion assessments showed no difference in perfusion in either the distal paw or tibialis anterior (TA) muscles (P>0.48 using two‐way ANOVA) between and control and PFKFB3‐treated mice. Ex vivo assessment of muscle contraction was performed in isolated extensor digitorum longus (EDL) muscles. Muscle cell specific expression of PFKFB3 significantly improved maximal force production following hindlimb ischemia (11.3 ± 2.6 N/cm2 vs. 6.1 ± 2.4 N/cm2 in AAV‐HSA‐GFP mice, P = 0.0147; Sham = 16.2 ± 2.4 N/cm2). Histological analysis of skeletal muscle confirmed a decrease in ischemic injury following AAV‐HSA‐PFKFB3 treatment.

CONCLUSIONS

These data demonstrate that PFKFB3‐mediated enhancement of glycolysis in the ischemic limb muscle is sufficient to induce a metabolic shift that protects against ischemic myopathy. Our results highlight a potential causal role for metabolism in the pathology that befalls the ischemic limb tissues.

Support or Funding Information

Supported by American Heart Association Grant 18CDA34110044 to TER.
Enteropathogenic Escherichia coli (EPEC) infection inhibits intestinal vitamin C transporter function and expression: in vitro and in vivo studies
Authors: Heskett Christopher W. , Teafatiller Trevor , Hennessey Carly , Gareau Melanie G. , Marchant Jonathan S. , Said Hamid M. , Subramanian Veedamali S.
Published: April 2020

Enteropathogenic Escherichia coli (EPEC) is a food‐borne pathogen and causes enteric illnesses in children. EPEC infection is often associated with malnutrition of the host, especially in individuals experiencing severe and prolonged infection, and/or in those who are nutritionally compromised. While EPEC infection impacts nutrient transporter function and expression in intestinal epithelial cells, to date the consequences of EPEC infection on intestinal absorption of ascorbic acid (AA) are not known. Therefore, we investigated this issue using human intestinal epithelial Caco‐2 cells (in vitro) and mouse (in vivo) models. Infecting Caco‐2 cells with EPEC (WT) markedly inhibited AA uptake. EPEC mutants (ΔescN, ΔespA, ΔespB and ΔespD) did not affect AA uptake, whereas ΔespF and ΔespG/G2 mutants significantly inhibited AA uptake in Caco‐2 cells. Further, we observed significantly reduced expression of both hSVCT1 and hSVCT2 protein and mRNA levels upon infection. Similarly, infecting mice with EPEC (WT) significantly inhibited AA uptake and also reduced the expression of both mSVCT1 and mSVCT2 protein and mRNA levels in jejunum and colon. Studies have shown that epigenetic mechanisms (microRNA) play a role in mediating responses to bacterial infection in the intestine. Therefore, we determined miR103a, miR141 and miR200a expression levels, which were recently shown to regulate SVCT1 and SVCT2. Data from in vitro and in vivo models showed that all three microRNAs were up‐regulated significantly upon EPEC infection. In addition, expression of the accessory protein human glyoxalate reductase/hydroxypyruvate reductase (hGRHPR), which regulates the SVCT1 function, was also markedly decreased by EPEC in both models. These findings suggest that in intestinal epithelial cells, EPEC infection markedly inhibits AA uptake via dysregulation of both SVCT1 and SVCT2 expression.

Support or Funding Information

Supported by NIH grants DK 107474, DK 58057, DK 56057, MH108154, GM088790, and a grant from the DVA
Elimination of the "essential" Warburg effect in mammalian cells through a multiplex genome engineering strategy
Authors: Lewis Nathan E.
Published: April 2020

Innovative genome editing technologies are accumulating and are rapidly elucidating the genetic basis of many cell functions. However, many disease phenotypes and physiological processes are governed by complex networks involving many gene products. Thus, numerous phenotypes need to be unraveled using multiplex genome editing techniques and in silico analysis. Furthermore, these approaches must further leverage legacy knowledge to identify the genes involved and understand the cell response. As an example, we unraveled the core cellular network controlling the Warburg effect, also known as aerobic glycolysis. This effect involves the tendency of rapidly‐proliferating cells to consume excess glucose and secrete copious amounts of lactic acid, despite having adequate oxygen for more efficient oxidative phosphorylation. This response is a hallmark of cancer, immune cell expansion, and other processes with rapidly proliferating cells. However, efforts to test the purpose of Warburg metabolism have been stymied by the difficulty to generate cell lines that are unable to produce lactic acid, since genes involved have proven to be essential or synthetic lethal in immortalized cells. We discovered a genetic circuit involving multiple genes that control lactic acid secretion, and using a multiplex genome editing with CRISPR, we successfully eliminated lactic acid secretion and enabled the deletion of multiple "essential" genes. Surprisingly, the cells show improved metabolic and growth phenotypes, despite the elimination of this fundamental metabolic activity. To understand how immortalized mammalian cells can cope without this seemingly essential metabolic process, we conducted a comprehensive analysis of these cell lines using time‐course RNA‐Seq, metabolomics, and analysis with a genome‐scale metabolic network model we have developed for Chinese hamster ovary cells1. Thus, through a multiplex metabolic engineering effort and comprehensive systems biology analysis, we have been able to engineer out a hallmark phenotype of proliferating cells and begin to understand now a cell can survive without a seemingly essential process.

Support or Funding Information

The Novo Nordisk Foundation Center for Biosustainability (NNF10CC1016517)
Elevated maternal linoleic acid alters placental fatty acids, nutrient transporters and inflammatory proteins
Authors: Hryciw Deanne Helena , Shrestha Nirajan , Sleep Simone , Cuffe James , Holland Olivia , Perkins Anthony , McAinch Andrew
Published: April 2020

Linoleic acid (LA) is the major omega‐6 fatty acid which is obtained from our diet. During pregnancy, LA is required for adequate fetal growth and development. For the growing fetus LA can only be obtained from the maternal diet, and is transferred from the maternal to fetal circulations by the placenta. At this time, in Western societies, we are overconsuming LA during pregnancy. Omega‐6 is metabolised by FADS1 and FADS2, which also metabiolise omega‐3. The ratio of omega‐6 to omega‐3 is important for human health, as they are proinflammatory and anti‐inflammatory, respectively. Therefore, the aim of this study is to determine if elevated maternal LA during pregnancy is alters placental fatty acids, nutrient transporter gene expression and inflammatory proteins.

Female Wistar Kyoto rats were fed a diet low in LA (LLA‐1.44% of energy) or diet high in LA (HLA‐6.21% of energy) for 10 weeks before and during gestation. Following mating with a male consuming normal chow, offspring and maternal rats were sacrificed at embryonic day (E)20, and placenta were collected for analysis of placental fatty acids, nutrient transporters and inflammatory markers.

In isolated placenta from pregnancies where mothers consumed an elevated LA diet, the concentration of LA was increased and the concentration of the omega‐3 fatty acid a‐linoleinic acid was decreased. Of interest, the downstream metabolite of LA, arachidonic acid was not altered in placenta from mothers consuming an elevated LA diet. mRNA expression of slc27a1 (fatty acid trasnport protein 1) was significantly downregulated in the male placenta from the dams fed with HLA, but not females. The mRNA expression of slc2a1 (glucose trasnporter 1) was significantly decreased in both male and female placenta from mothers fed the HLA diet. Further, the protein concentration of interleukin‐7 (IL‐7) was significantly decreased in both male and female placenta (labyrinth) from the dams fed with HLA, however there were no changes in protein expression of IL‐6 and TNF‐α in the labyrinth.

In conclusion, a maternal diet high in LA alters fatty acid concentrations, nutrient transporters and inflammatory cytokines in the placenta. The consequences of this on offspring development, and therefore long term health require further investigation.

Support or Funding Information

Allen Foundation (USA)
The challenges of adolescent sleep
Authors: Illingworth Gaby
Published: April 2020

Sleep is vital for our physical, emotional and cognitive health. However, adolescents face many challenges where their sleep is concerned. This is reflected in their sleep patterns including the timing of their sleep and how much sleep they achieve on a regular basis: their sleep is characteristically delayed and short. Notably, insufficient sleep is associated with impairments in adolescent functioning. Endogenous and exogenous factors are known to affect sleep at this age. Alterations in the bioregulation of sleep, comprising the circadian timing system and the sleep/wake homeostatic system, represent the intrinsic mechanisms at work. Compounding this, environmental, psychosocial and lifestyle factors may contribute to shortened sleep. This review discusses the amount of sleep gained by adolescents and its implications, the challenges to adolescent sleep and the interventions introduced in an effort to prioritize sleep health in this important developmental period.
Auraticoccus cholistanensis sp. nov., an actinomycete isolated from soil of the Cholistan Desert, and emended description of the genus Auraticoccus
Authors: Cheema Mohsin Tassawar , Ye Jing-Jing , Li Fei-Na , Lu Qin-Pei , Abbas Muhammad , Sajid Imran , Huang Da-Lin , Liu Shao-Wei , Sun Cheng-Hang
Published: April 2020

A Gram-stain-positive, aerobic, non-motile and non-spore-forming actinobacterium, designated as F435T, was isolated from soil sample collected from the Cholistan Desert, Pakistan. The taxonomic position of the strain was established by using a polyphasic taxonomic approach. The cells were coccoid-shaped and found in single or arrangement of pairs. The novel strain grew at 15‒37 °C (optimum, 25‒30 °C), pH 7‒11 (optimum, pH 7–8) and in the presence of 0‒8% (w/v) NaCl (optimum, 0 %). Results of blast analysis based on 16S rRNA gene sequences showed that

Auraticoccus monumenti

MON 2.2T was its closest relative with 97.4 % similarity followed by

Desertihabitans aurantiacus

CPCC 204711T (95.2 %). In phylogenetic trees, strain F435T formed a robust cluster with the only member of the genus

Auraticoccus

. The peptidoglycan isomer present in the cell wall was ll-diaminopimelic acid. The major fatty acid was determined to be anteiso-C15 : 0. Characteristic polar lipids of the strain were diphosphatidylglycerol, phosphatidylglycerol, phosphoglycolipids and glycolipids. The predominant menaquinone was MK-9(H4). The genomic G+C content was calculated as 73.5 mol%. The digital DNA–DNA hybridization (GGDC) and average nucleotide identity (ANI) values between strain F435T and

A. monumenti

MON 2.2T were 24.6 and 81.8 %, respectively. Based on the results of phenotypic, chemotaxonomic, phylogenetic and phylogenomic analyses, strain F435T represents a novel specie of the genus

Auraticoccus

, for which the name Auraticoccus cholistanensis sp. nov. is proposed. The type strain is F435T (=JCM 33648T=CGMCC 1.17443T). The description of the genus

Auraticoccus

has also been emended.
Identification of Photorhabdus symbionts by MALDI-TOF MS
Authors: Hill Virginia , Kuhnert Peter , Erb Matthias , Machado Ricardo A. R.
Published: April 2020

Species of the bacterial genus Photorhabus live in a symbiotic relationship with Heterorhabditis entomopathogenic nematodes. Besides their use as biological control agents against agricultural pests, some

Photorhabdus

species are also a source of natural products and are of medical interest due to their ability to cause tissue infections and subcutaneous lesions in humans. Given the diversity of

Photorhabdus

species, rapid and reliable methods to resolve this genus to the species level are needed. In this study, we evaluated the potential of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the identification of

Photorhabdus

species. To this end, we established a collection of 54 isolates consisting of type strains and multiple field strains that belong to each of the validly described species and subspecies of this genus. Reference spectra for the strains were generated and used to complement a currently available database. The extended reference database was then used for identification based on the direct transfer sample preparation method and the protein fingerprint of single colonies. High-level discrimination of distantly related species was observed. However, lower discrimination was observed with some of the most closely related species and subspecies. Our results therefore suggest that MALDI-TOF MS can be used to correctly identify

Photorhabdus

strains at the genus and species level, but has limited resolution power for closely related species and subspecies. Our study demonstrates the suitability and limitations of MALDI-TOF-based identification methods for assessment of the taxonomic position and identification of

Photorhabdus

isolates.
Relationship between COVID-19 death toll doubling time and national BCG vaccination policy
Authors: Akiyama Yutaka , Ishida Takashi
Published: April 2020

In this manuscript, we showed a statistically significant difference of the doubling times of the death toll between the group of countries with national universal Bacillus Calmette-Guerin (BCG) vaccination and the group without it for recent years. Based on a statistical test, the distributions of the doubling time of these two groups were significantly different (p=0.007). Miller et al. reported the relationship between BCG vaccination and mortality for COVID-19 based on deaths per million inhabitants. However, they did not take into account the differences in COVID-19 detection rates among the countries and the epidemic stages of the countries. Therefore we used a doubling time of the death toll as a more stable indicator instead. We also investigated the dependency of the BCG strains. Among the 42 BCG-vaccinated countries, the median doubling time of the eight countries using “Tokyo 172-1” strain at least partially (Japan, Iraq, Malaysia, South Korea, Philippines, Saudi Arabia, Pakistan, and Bangladesh) was 7.2 days, and that of the other 34 vaccinated countries was 5.5 days. Their distributions were also significantly different (p=0.026).
Hybrid Machine Learning Model of Extreme Learning Machine Radial basis function for Breast Cancer Detection and Diagnosis; a Multilayer Fuzzy Expert System
Authors: Mojrian Sanaz , Pinter Gergo , Joloudari Javad Hassannataj , Felde Imre , Szabo-Gali Akos , Nadai Laszlo , Mosavi Amir
Published: April 2020

Mammography is often used as the most common laboratory method for the detection of breast cancer, yet associated with the high cost and many side effects. Machine learning prediction as an alternative method has shown promising results. This paper presents a method based on a multilayer fuzzy expert system for the detection of breast cancer using an extreme learning machine (ELM) classification model integrated with radial basis function (RBF) kernel called ELM-RBF, considering the Wisconsin dataset. The performance of the proposed model is further compared with a linear-SVM model. The proposed model outperforms the linear-SVM model with RMSE, R2, MAPE equal to 0.1719, 0.9374 and 0.0539, respectively. Furthermore, both models are studied in terms of criteria of accuracy, precision, sensitivity, specificity, validation, true positive rate (TPR), and false-negative rate (FNR). The ELM-RBF model for these criteria presents better performance compared to the SVM model.
Multiscale 3-dimensional pathology findings of COVID-19 diseased lung using high-resolution cleared tissue microscopy
Authors: Li Guang , Fox Sharon E. , Summa Brian , Hu Bihe , Wenk Carola , Akmatbekov Aibek , Harbert Jack L. , Vander Heide Richard S. , Brown J. Quincy
Published: April 2020

The study of pulmonary samples from individuals who have died as a direct result of COVID-19 infection is vital to our understanding of the pathogenesis of this disease. Histopathologic studies of lung tissue from autopsy of patients with COVID-19 specific mortality are only just emerging. All existing reports have relied on traditional 2-dimensional slide-based histological methods for specimen preparation. However, emerging methods for high-resolution, massively multiscale imaging of tissue microstructure using fluorescence labeling and tissue clearing methods enable the acquisition of tissue histology in 3-dimensions, that could open new insights into the nature of SARS-Cov-2 infection and COVID-19 disease processes. In this article, we present the first 3-dimensional images of lung autopsy tissues taken from a COVID-19 patient, including 3D “virtual histology” of cubic-millimeter volumes of the diseased lung, providing unique insights into disease processes contributing to mortality that could inform frontline treatment decisions.
BCG VACCINES MAY NOT REDUCE COVID-19 MORTALITY RATES
Authors: Singh Samer
Published: April 2020

The reason for the observed country-wise variability in incidence and severity of the COVID-19 outcome remains unknown. Few recent studies have suggested a positive protective correlation of the BCG vaccination policy of the countries with the observed COVID-19 severity. The current study was undertaken to reassess the existing data as of 4th April 2020. The incidence rates (cases per million population), Case Fatality Rates (CFR) and inherently more robust Infection Fatality Rates (IFR) were calculated across countries accounting for about 99% COVID-19 deaths. The initial scrutiny suggested a weaker association with BCG vaccination policy or BCG coverage, so positivity to the Tuberculin Sensitivity Test (TST)/ Interferon Gamma Release Assay (IGRA) as a measure of the potential protective effect of the resident populations’ exposure to Mycobacterium spp. whether from BCG vaccination or as a result of exposure to environmental mycobacteria was analyzed. The incidence rates (the number of cases per million population) decreased with an increase in % LTBI (TST/IGRA positivity) for the analyzed countries with R2 =0.6343, suggesting an exponentially negative covariation. However, the covariation of CFR estimates that ranged from 0.29% to 12.25 % (average 5.39%) among countries, was tenuous. Interim estimates of IFR (i-IFR), a more dependable measure for such studies, for the best and worst-case scenarios, i.e., i-IFR-l and i-IFR-h, predict on an average 20.57% to 30.15 % COVID-19 fatality rates globally, but individual country estimates display huge variation. Among countries accounting for 92.14% deaths (11 countries; top 20% countries included in current study) the estimate for lowest IFRs (i-IFR-l=4.16 (China) & i-IFR-h=4.61 (China)) and highest IFRs (i-IFR-l=96.39% (UK); & i-IFR-h=96.54% (UK)) displayed huge difference (average for the group: CFR=6.8±3.6%; i-IFR-l=34.97±30.55%; & i-IFR-h=44.20±29.08%). Currently, the worst affected countries Italy (CFR=12.25%; i-IFR-l=42.63%; i-IFR-h=48.69%) and Spain (CFR=9.39%; i- IFR-l=26.85%; i-IFR-h=36.60%) would seemingly cope with COVID-19 better than UK, Netherlands and USA while the countries Germany (CFR=1.40%; i-IFR-l=4.93%; i-IFR-h=17.49%) and Switzerland (CFR=3.01%; i-IFR-l=10.87%; i-IFR-h=16.23%) along with China could fare the best. The rest of the 80% countries (accounting for 6.74% deaths), seemed to have reduced mortality (CFR=2.45±2.01; i-IFR-l= 30.62±28.24%; i-IFR-h=40.99±30.47%) with associated high % LTBI (17.28±8.87) than top 20% countries. The inherent issues in the data set (e.g., heterogeneity, non- random sampling, different criteria of sampling and reporting, access to health care, genetic composition, underlying co-morbidities, etc) need to be taken into account for making informed decisions.
Serum Mycoplasma pneumoniae IgG in COVID-19: A Protective Factor
Authors: Mi Bobin , Chen Lang , Panayi Adriana C. , Xiong Yuan , Liu Guohui
Published: April 2020

Background

A correlation between prior exposure to Mycoplasma pneumoniae (IgG positive) and better clinical response to COVID-19 was elusive.

Methods

A retrospective review of all COVID-19 infected patients treated at Wuhan Union Hospital from Feb 1 to Mar 20 was carried out. Continuous variables were described as mean, median, and interquartile range (IQR), while categorical variables were compared by X2 test or Fisher’s exact test between COVID-19 infected patients with mycoplasma lgG (-) and mycoplasma lgG (+).

Results

Statistically significant differences were shown in terms of laboratory test results. COVID-19 infected patients with mycoplasma lgG positivity had a higher lymphocyte count and percentage (p=0.026, p=0.017), monocyte count and percentage (p=0.028, p=0.006) and eosinophil count and percentage (p=0.039, p=0.007), and a lower neutrophil count and percentage (p=0.044, p=0.006) than COVID-19 infected patients without mycoplasma lgG. Other routine blood tests, including coagulation tests, blood biochemistry and infection-related biomarkers did not significantly differ except for thrombin time (p=0.001) and lactate dehydrogenase (p=0.008). Furthermore, requirement and use of a nasal catheter or oxygen mask was significantly lower in COVID-19 infected patients with mycoplasma lgG positivity (p=0.029).

Conclusions

Our findings indicate that mycoplasma IgG positivity is a potential protective factor for SARS-CoV-2 infection.
Immediate and Near Future Prediction of COVID-19 Patients in the U.S. Population Aged 65+ With the Prior Medical Conditions of Hypertension, Cardiovascular and Lung Diseases: Methods, Models and Acute Care Estimates
Authors: Srinivasa Rao Arni S.R. , Miller Douglas D. , Berman Adam E. , Hess David C. , Krantz Steven G.
Published: April 2020

Importance

Given the rapid rise of COVID-19 cases in the U.S. during March 2020 there has been a severe burden on the health care systems and care providers in the country. The impact of the virus so far was higher on the population aged 65+. Hospitalizations were higher among those with underlying medical conditions, namely, hypertension, cardiovascular and lung diseases. Hence, to have an idea of the number of new COVID-19 infections among these high-risk populations that could occur in the short-term could assist promptly to the country’s health care system for immediate health care planning. These estimates may aid us in better understanding the potential volumes of patients requiring inpatient care.

Objective

To provide immediate and short-term model-based predictions of COVID-19 patients in the U.S. population aged 65+ during April-June, 2020, those with the prior medical conditions of hypertension, cardiovascular and lung diseases.

Design, Setting, and Participants

We developed age-structured dynamic mathematical combined with wavelet analysis to understand the number of new cases that may emerge in the U.S. population aged 65+. We have estimated the number of people aged 65+ who might have three underlying conditions mentioned and a possible number of hospitalizations among them due to COVID-19 if they get infected. We have used publicly available data sources for developing our framework and estimates.

Results

We estimate that there are 13 million individuals aged 65+ who have one or a combination of three major prior medical conditions in the U.S. who need to be protected against COVID-19 to reduce a large number of hospitalizations and associated deaths. Hospitalizations of patients both with and without ICU-admissions with more prevalent underlying conditions could range between 31,633 (20,310 non-ICU hospitalizations and 11,323 ICU-admissions) to 94,666 (60,779 non-ICU hospitalizations and 33,866 ICU-admissions) cases during the same period. Under a rapid spread of the virus environment, these hospitalizations could be beyond 430,000 within the above three-month period.

Conclusions and Relevance

COVID-19 continues to dramatically and adversely affect the lives of people aged 65+ in the U.S. During the next three months which could result in thousands of hospitalizations if precautions against the virus spread are not implemented and adhered to.
An SEIR Model for Assessment of Current COVID-19 Pandemic Situation in the UK
Authors: Sun Peiliang , Li Kang
Published: April 2020

Abstract

The ongoing COVID-19 pandemic spread to the UK in early 2020 with the first few cases being identified in late January. A rapid increase in confirmed cases started in March, and the number of infected people is however unknown, largely due to the rather limited testing scale. A number of reports published so far reveal that the COVID-19 has long incubation period, high fatality ratio and non-specific symptoms, making this novel coronavirus far different from common seasonal influenza. In this note, we present a modified SEIR model which takes into account the time lag effect and probability distribution of model states. Based on the proposed model, it is estimated that the actual total number of infected people by 1 April in the UK might have already exceeded 610,000. Average fatality rates under different assumptions at the beginning of April 2020 are also estimated. Our model also reveals that the R0 value is between 7.5–9 which is much larger than most of the previously reported values. The proposed model has a potential to be used for assessing future epidemic situations under different intervention strategies.
Evaluation of lockdown impact on SARS-CoV-2 dynamics through viral genome quantification in Paris wastewaters
Authors: Wurtzer S , Marechal V , Mouchel JM , Maday Y , Teyssou R , Richard E , Almayrac JL , Moulin L
Published: April 2020

SARS-CoV-2 is the etiological agent of COVID-19. Most of SARS-CoV-2 carriers are assumed to exhibit no or mild non-specific symptoms. Thus, they may contribute to the rapid and mostly silent circulation of the virus among humans. Since SARS-CoV-2 can be detected in stool samples it has recently been proposed to monitor SARS-CoV-2 in wastewaters (WW) as a complementary tool to investigate virus circulation in human populations. In the present work we assumed that the quantification of SARS-CoV-2 genomes in wastewaters should correlate with the number of symptomatic or non-symptomatic carriers. To test this hypothesis, we performed a time-course quantitative analysis of SARS-CoV-2 by RT-qPCR in raw wastewater samples collected from several major wastewater treatment plant (WWTP) of the Parisian area. The study was conducted from 5 March to 23 April 2020, therefore including the lockdown period in France (since 17 March 2020). We confirmed that the increase of genome units in raw wastewaters accurately followed the increase of human COVID-19 cases observed at the regional level. Of note, the viral genomes could be detected before the beginning of the exponential growth of the epidemic. As importantly, a marked decrease in the quantities of genomes units was observed concomitantly with the reduction in the number of new COVID-19 cases which was an expected consequence of the lockdown. A s a conclusion, this work suggests that a quantitative monitoring of SARS-CoV-2 genomes in wastewaters should bring important and additional information for an improved survey of SARS-CoV-2 circulation at the local or regional scale.
Estimation of airborne viral emission: quanta emission rate of SARS-CoV-2 for infection risk assessment
Authors: Buonanno G. , Stabile L. , Morawska L.
Published: April 2020

Airborne transmission is a pathway of contagion that is still not sufficiently investigated despite the evidence in the scientific literature of the role it can play in the context of an epidemic. While the medical research area dedicates efforts to find cures and remedies to counteract the effects of a virus, the engineering area is involved in providing risk assessments in indoor environments by simulating the airborne transmission of the virus during an epidemic. To this end, virus air emission data are needed. Unfortunately, this information is usually available only after the outbreak, based on specific reverse engineering cases. In this work, a novel approach to estimate the viral load emitted by a contagious subject on the basis of the viral load in the mouth, the type of respiratory activity (e.g. breathing, speaking), respiratory physiological parameters (e.g. inhalation rate), and activity level (e.g. resting, standing, light exercise) is proposed. The estimates of the proposed approach are in good agreement with values of viral loads of well-known diseases from the literature. The quanta emission rates of an asymptomatic SARS-CoV-2 infected subject, with a viral load in the mouth of 108 copies mL−1, were 10.5 quanta h−1 and 320 quanta h−1 for breathing and speaking respiratory activities, respectively, at rest. In the case of light activity, the values would increase to 33.9 quanta h−1 and 1.03×103 quanta h−1, respectively.

The findings in terms of quanta emission rates were then adopted in infection risk models to demonstrate its application by evaluating the number of people infected by an asymptomatic SARS-CoV-2 subject in Italian indoor microenvironments before and after the introduction of virus containment measures. The results obtained from the simulations clearly highlight that a key role is played by proper ventilation in containment of the virus in indoor environments.
Pathologic Nodal Upstaging Predictive Models for CT-based Clinical Node Negative Non-Small Cell Lung Cancer
Authors: Chong Weelic , Hai Yang , Zhou Jian , Liu Lun-xu
Published: April 2020

Background

Accurate clinical nodal staging of non-small cell lung cancer (NSCLC) is essential for surgical management. Some clinical node negative cases diagnosed preoperatively by CT were later staged as pathological N1 (pN1) or pN2. Our study aimed to evaluate factors related to pathological nodal upstaging and develop statistical models for predicting upstaging.

Methods

We retrospectively reviewed 1,735 patients with clinical node negative NSCLC from 2011 to 2016 in the West China Lung Cancer database. Demographic and clinical data were analyzed via univariate and multivariate approaches. Predictive models were developed on a training set and validated with independent datasets.

Results

171 (9.9%) clinical node negative patients have pathologic nodal upstaging to pN1. 191(11.0%) patients were upstaged to p(N1+N2). 91(5.2%) patients have pSN2 pathologic nodal upstaging. Preoperative factors were used to establish 3 statistical models for predicting pathological nodal upstaging. The area under the receiver operator characteristic (AUC) were 0.815, 0.768, and 0.726, for pN1, p(N1+N2) and pSN2 respectively.

Conclusion

Our models may help evaluate the possibility of nodal upstaging for clinical node negative NSCLC and enable surgeons to form appropriate plans preoperatively. External validation in a prospective multi-site study is needed before adoption into clinical practice.
Differential Effects of Pathological Beta Burst Dynamics Between Parkinson’s Disease Phenotypes Across Different Movements
Authors: Neuville Raumin S. , Petrucci Matthew N. , Wilkins Kevin B. , Anderson Ross. W. , Hoffman Shannon L. , Parker Jordan E. , Velisar Anca , Bronte-Stewart Helen M.
Published: April 2020

Background

Resting state beta band (13 – 30 Hz) oscillations represent pathological neural activity in Parkinson’s disease (PD). It is unknown how the peak frequency or dynamics of beta oscillations may change among fine, limb and axial movements and different disease phenotypes. This will be critical for the development of personalized closed loop deep brain stimulation (DBS) algorithms during different activity states.

Methods

Subthalamic (STN) local field potentials (LFPs) were recorded from a sensing neurostimulator (Activa® PC+S, Medtronic PLC.,) in fourteen PD participants (six tremor-dominant, 8 akinetic-rigid) off medication/off STN DBS during thirty seconds of repetitive alternating finger tapping, wrist-flexion extension, stepping in place, and free walking. Beta power peaks and beta burst dynamics were identified by custom algorithms and were compared among movement tasks and between tremor-dominant and akinetic-rigid groups.

Results

Beta power peaks were evident during fine, limb, and axial movements in 98% of movement trials; the peak frequencies were similar during each type of movement. Burst power and duration were significantly larger in the high beta band, but not in the low beta band, in the akinetic-rigid group compared to the tremor-dominant group.

Conclusions

The conservation of beta peak frequency during different activity states supports the feasibility of patient-specific closed loop DBS algorithms driven by the dynamics of the same beta band during different activities. Akinetic-rigid participants had greater power and longer burst durations in the high beta band than tremor-dominant participants during movement, which may relate to the difference in underlying pathophysiology between phenotypes.
Association between gene expression profiling of skin lesion and autoantibody in patients with systemic sclerosis
Authors: Inamo Jun
Published: April 2020

Objective

The aim of this study was to investigate relevance between type of autoantibody and gene expression profile in skin lesion of systemic sclerosis (SSc), and identify specifically dysregulated pathways.

Methods

Sixty-one patients with SSc from the Genetics versus Environment in Scleroderma Outcome Study cohort and thirty-six healthy controls (HC) are included. Differentially expressed genes (DEGs) were extracted and functional enrichment and pathways analysis were conducted.

Results

Compared with HC, lists consisting of 2, 71, 10, 144 and 78 DEGs were created for patients without specific autoantibody, anti-centromere (ACA), anti-U1 RNP (RNP), anti-RNA polymerase III (RNAP) and anti-topoisomerase I (ATA) antibody, respectively. While part of enriched pathways overlapped, distinct pathways were identified except those without specific autoantibody: keratinocyte differentiation in ACA, NF-kB signaling and cellular response to transforming growth factor beta stimulus in RNAP, interferon alpha/beta signaling of RNP and cellular response to stress in ATA.

Conclusion

Pathogenic pathways were identified according to type of autoantibodies by leveraging gene expression data of patients and controls from multi-center cohort. The current study will promote to explore new therapeutic target for SSc.

Key message

Distinct pathways are associated with type of autoantibody in skin lesion of systemic sclerosis.
Detection of neutralising antibodies to SARS coronavirus 2 to determine population exposure in Scottish blood donors between March and May 2020
Authors: Thompson CP. , Grayson N. , Paton R.S. , Bolton J. , Lourenco J. , Penman BS. , Lee L. , Odon V. , Mongkolsapaya J. , Chinnakannan S. , Dejnirattisai W. , Edmans M. , Fyfe A. , Imlach C. , Kooblall K. , Lim N. , Liu C. , Lopez-Camacho C. , McInally C. , McNaughton A.L. , Ramamurthy N. , Ratcliff J. , Supasa P. , Sampson O. , Wang B. , Mentzer A. , Turner M. , Semple M.G. , Baillie J.K. ,   ISARIC4C Investigators, Harvala H. , Screaton G.R. , Temperton N. , Klenerman P. , Jarvis L.M. , Gupta S. , Simmonds P.
Published: April 2020

Background

The progression and geographical distribution of SARS coronavirus 2 (SARS-CoV-2) infection in the UK and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland between the 17th of March and the 18th of May to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression.

Aim

To determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic.

Methods

A pseudotyped SARS-CoV-2 virus microneutralisation assay was used to detect neutralising antibodies to SARS-CoV-2. The study group comprised samples from 3,500 blood donors collected in Scotland between the 17th of March and 19th of May, 2020. Controls were collected from 100 donors in Scotland during 2019.

Results

All samples collected on the 17th March, 2020 (n=500) were negative in the pseudotyped SARS-CoV-2 virus microneutralisation assay. Neutralising antibodies were detected in 6/500 donors from the 23th-26th of March. The number of samples containing neutralising antibodies did not significantly rise after the 5th-6th April until the end of the study on the 18th of May. We find that infections are concentrated in certain postcodes indicating that outbreaks of infection are extremely localised. In contrast, other areas remain comparatively untouched by the epidemic.

Conclusion

These data indicate that sero-surveys of blood banks can serve as a useful tool for tracking the emergence and progression of an epidemic like the current SARS-CoV-2 outbreak.
A vulnerability-based approach to human-mobility reduction for countering COVID-19 transmission in London while considering local air quality
Authors: Sasidharan Manu , Singh Ajit , Torbaghan Mehran Eskandari , Parlikad Ajith Kumar
Published: April 2020

An ecologic analysis was conducted to explore the correlation between air pollution, and COVID-19 cases and fatality rates in London. The analysis demonstrated a strong correlation (R2>0.7) between increment in air pollution and an increase in the risk of COVID-19 transmission within London boroughs. Particularly, strong correlations (R2>0.72) between the risk of COVID-19 fatality and NO2 and PM2.5 pollution concentrations were also found. Although this study assumed the same level of air pollution across a particular London borough, it demonstrates the possibility to employ air pollution as an indicator to rapidly identify the city’s vulnerable regions. Such an approach can inform the decisions to suspend or reduce the operation of different public transport modes within a city. The methodology and learnings from the study can thus aid in public transport’s response to COVID-19 outbreak by adopting different levels of human-mobility reduction strategies based on the vulnerability of a given region.

One Sentence Summary

This study introduces air pollution levels as an indicator for a region’s vulnerability to COVID-19 and suggests human-mobility reduction measures.
Time-variant strategies for optimizing the performance of non-pharmaceutical interventions (NPIs) in protecting lives and livelihoods during the COVID-19 pandemic
Authors: Aun Yap Wei , Raja Dhesi Baha
Published: April 2020

A stochastic Individual Contact Model (ICM) using SIR compartments allowing for time-variant parameters was used to simulate 100 non-pharmaceutical intervention (NPI) strategies and exit trajectories for a hypothetical population, and to collect epidemiological and non-epidemiological outcomes to measure the performance of these strategies over the course of a period of intervention (up to six months) for a total duration of one-year to allow the full implications of the strategy and endgame to manifest. We find that variations in the time dimension and intensity of various strategies can have vastly different performance outcomes: (i) the timing of NPIs can ‘shrink the area under the curve’ (cumulative infections) not just ‘flatten the curve’; (ii) prolonged lockdowns have diminishing margins of returns; (iii) smooth, submaximal lockdowns perform better than pulsatile lockdowns; and (iv) the efficiency of various strategies incorporating both epidemiological and non-epidemiological outcomes vary substantially. Most sobering, none of the simulated strategies allow for an ‘acceptable’ path to exit within six months due to very large gaps in health system capacity.
A Predictive Model for the Evolution of COVID-19
Authors: Bhardwaj Rajneesh
Published: April 2020

We predict the evolution of the COVID-19 pandemic in several countries by using a regression-based predictive model. In particular, the growth rate of the infection has been fitted as an exponential decay, as compared to a linear decay, reported previously. The model has been validated with the data of China and South Korea, where the pandemic is nearing to its end. The data of Italy, Germany, Spain, and Sweden show that the peak of the infection has reached i.e. a time when the new infections will start to decrease as compared to the previous day. The model predicts the approximate number of total infections at the end of the outbreak. The model prediction of the USA, and Brazil show that the peak will reach in the next two-three weeks. The total number of infections in the USA is estimated to be around 4 million by the model. The reported data of India show the start of disease evolution, with a large initial scatter in the growth rate. The possible peak date and the total number of infections are predicted using the data available.