bluuebunny/crossref_metadata_2025 huggingface dataset:
Actions of colony-stimulating factor 3 on the maturing oocyte and developing embryo in cattle
Authors: Jannaman Elizabeth A , Xiao Yao , Hansen Peter J
Published: April 2020

Colony-stimulating factor 3 (CSF3), also known as granulocyte colony-stimulating factor, is used to reduce the incidence of mastitis in cattle. Here, we tested whether recombinant bovine CSF3 at 1, 10, or 100 ng/mL acts on the bovine oocyte during maturation or on the developing embryo to modify competence for development and characteristics of the resultant blastocyst. For experiment 1, oocytes were matured with or without CSF3. The resultant embryos were cultured in a serum-free medium for 7.5 d. There was no effect of CSF3 on cleavage or on development to the blastocyst stage except that 100 ng/mL reduced the percent of putative zygotes and cleaved embryos becoming blastocysts. Expression of transcripts for 93 genes in blastocysts was evaluated by RT-PCR using the Fluidigm platform. Transcript abundance was affected by one or more concentrations of CSF3 for four genes only (CYP11A1, NOTCH2, RAC1, and YAP1). For experiment 2, cumulus-oocyte complexes (COC) were fertilized with either X- or Y-sorted semen. Putative zygotes were cultured in medium containing CSF3 treatments added at the beginning of culture. There was no effect of CSF3, sex, or the interaction on the percent of putative zygotes that cleaved or on the percent of putative zygotes or cleaved embryos becoming a blastocyst. For experiment 3, CSF3 was added from day 4 to 7.5 of development. There was no effect of CSF3 on development to the blastocyst stage. Transcript abundance of 10 genes was increased by 100 ng/mL CSF3, including markers of epiblast (NANOG, SOX2), hypoblast (ALPL, FN1, KDM2B, and PDGFRA), epiblast and hypoblast (HNF4A) and trophectoderm (TJAP1). Results are indicative that concentrations of CSF3 higher than typical after therapeutic administration can reduce oocyte competence and act on the embryo to affect characteristics of the blastocyst.
Fibro-osseous pseudotumour of the digit—a diagnostic challenge
Authors: Rela Mariam , Bantick Giles
Published: April 2020

A 60-year-old right-hand dominant woman presented to the emergency department with a 3-week history of pain and swelling in her right thumb. The X-ray showed evidence of erosion at the tip of the distal phalanx. Her initial management included surgical debridement with bone biopsies and intravenous antibiotics. The initial working diagnosis was a soft tissue infection of the thumb tip, causing osteomyelitis of the distal phalanx. The X-ray findings also raised the suspicion of a possible bone tumour. She was treated as having osteomyelitis and attended ambulatory care for daily intravenous antibiotics for 2 weeks. Initial histology was reported as a spindle cell tumour; however, following discussion at the sarcoma MDT, a diagnosis of a fibro-osseous pseudotumour of the digit was made. This is a benign lesion that was managed non-operatively in this patient. This case emphasises the importance of considering all differential diagnoses, even in a common presentation.
Mitigating yellow-fever-vaccine-associated viscerotropic disease in older travellers
Authors: Fletcher Rachael , Simons Hilary , Patel Dipti
Published: April 2020

Following two recent fatal yellow fever vaccine associated adverse reactions, a review of the safety of the yellow fever vaccine was undertaken in the UK. While the review found the administration of yellow fever vaccine remained favourable for most travellers, when used as indicated, a number of changes to clinical practice were mandated.
Allopolyploid Speciation Accompanied by Gene Flow in a Tree Fern
Authors: Wang Jing , Dong Shiyong , Yang Lihua , Harris Aj , Schneider Harald , Kang Ming
Published: April 2020

Hybridization in plants may result in hybrid speciation or introgression and, thus, is now widely understood to be an important mechanism of species diversity on an evolutionary timescale. Hybridization is particularly common in ferns, as is polyploidy, which often results from hybrid crosses. Nevertheless, hybrid speciation as an evolutionary process in fern lineages remains poorly understood. Here, we employ flow cytometry, phylogeny, genomewide single nucleotide polymorphism data sets, and admixture and coalescent modeling to show that the scaly tree fern, Gymnosphaera metteniana is a naturally occurring allotetraploid species derived from hybridization between the diploids, G. denticulata and G. gigantea. Moreover, we detected ongoing gene flow between the hybrid species and its progenitors, and we found that G. gigantea and G. metteniana inhabit distinct niches, whereas climatic niches of G. denticulata and G. metteniana largely overlap. Taken together, these results suggest that either some degree of intrinsic genetic isolation between the hybrid species and its parental progenitors or ecological isolation over short distances may be playing an important role in the evolution of reproductive barriers. Historical climate change may have facilitated the origin of G. metteniana, with the timing of hybridization coinciding with a period of intensification of the East Asian monsoon during the Pliocene and Pleistocene periods in southern China. Our study of allotetraploid G. metteniana represents the first genomic-level documentation of hybrid speciation in scaly tree ferns and, thus, provides a new perspective on evolution in the lineage.
A Whole-Genome Scan for Association with Invasion Success in the Fruit Fly Drosophila suzukii Using Contrasts of Allele Frequencies Corrected for Population Structure
Authors: Olazcuaga Laure , Loiseau Anne , Parrinello Hugues , Paris Mathilde , Fraimout Antoine , Guedot Christelle , Diepenbrock Lauren M , Kenis Marc , Zhang Jinping , Chen Xiao , Borowiec Nicolas , Facon Benoit , Vogt Heidrun , Price Donald K , Vogel Heiko , Prud’homme Benjamin , Estoup Arnaud , Gautier Mathieu
Published: April 2020

Evidence is accumulating that evolutionary changes are not only common during biological invasions but may also contribute directly to invasion success. The genomic basis of such changes is still largely unexplored. Yet, understanding the genomic response to invasion may help to predict the conditions under which invasiveness can be enhanced or suppressed. Here, we characterized the genome response of the spotted wing drosophila Drosophila suzukii during the worldwide invasion of this pest insect species, by conducting a genome-wide association study to identify genes involved in adaptive processes during invasion. Genomic data from 22 population samples were analyzed to detect genetic variants associated with the status (invasive versus native) of the sampled populations based on a newly developed statistic, we called C2, that contrasts allele frequencies corrected for population structure. We evaluated this new statistical framework using simulated data sets and implemented it in an upgraded version of the program BayPass. We identified a relatively small set of single-nucleotide polymorphisms that show a highly significant association with the invasive status of D. suzukii populations. In particular, two genes, RhoGEF64C and cpo, contained single-nucleotide polymorphisms significantly associated with the invasive status in the two separate main invasion routes of D. suzukii. Our methodological approaches can be applied to any other invasive species, and more generally to any evolutionary model for species characterized by nonequilibrium demographic conditions for which binary covariables of interest can be defined at the population level.
Structural Phylogenetics with Confidence
Authors: Malik Ashar J , Poole Anthony M , Allison Jane R
Published: April 2020

For evaluating the deepest evolutionary relationships among proteins, sequence similarity is too low for application of sequence-based homology search or phylogenetic methods. In such cases, comparison of protein structures, which are often better conserved than sequences, may provide an alternative means of uncovering deep evolutionary signal. Although major protein structure databases such as SCOP and CATH hierarchically group protein structures, they do not describe the specific evolutionary relationships within a hierarchical level. Structural phylogenies have the potential to fill this gap. However, it is difficult to assess evolutionary relationships derived from structural phylogenies without some means of assessing confidence in such trees. We therefore address two shortcomings in the application of structural data to deep phylogeny. First, we examine whether phylogenies derived from pairwise structural comparisons are sensitive to differences in protein length and shape. We find that structural phylogenetics is best employed where structures have very similar lengths, and that shape fluctuations generated during molecular dynamics simulations impact pairwise comparisons, but not so drastically as to eliminate evolutionary signal. Second, we address the absence of statistical support for structural phylogeny. We present a method for assessing confidence in a structural phylogeny using shape fluctuations generated via molecular dynamics or Monte Carlo simulations of proteins. Our approach will aid the evolutionary reconstruction of relationships across structurally defined protein superfamilies. With the Protein Data Bank now containing in excess of 158,000 entries (December 2019), we predict that structural phylogenetics will become a useful tool for ordering the protein universe.
The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridiumdifficile Infection: Current Understanding and Gap Analysis
Authors: Wilcox Mark H , McGovern Barbara H , Hecht Gail A
Published: April 2020

The leading risk factor for Clostridioides (Clostridium) difficile infection (CDI) is broad-spectrum antibiotics, which lead to low microbial diversity, or dysbiosis. Current therapeutic strategies for CDI are insufficient, as they do not address the key role of the microbiome in preventing C. difficile spore germination into toxin-producing vegetative bacteria, which leads to symptomatic disease. Fecal microbiota transplant (FMT) appears to reduce the risk of recurrent CDI through microbiome restoration. However, a wide range of efficacy rates have been reported, and few placebo-controlled trials have been conducted, limiting our understanding of FMT efficacy and safety. We discuss the current knowledge gaps driven by questions around the quality and consistency of clinical trial results, patient selection, diagnostic methodologies, use of suppressive antibiotic therapy, and methods for adverse event reporting. We provide specific recommendations for future trial designs of FMT to provide improved quality of the clinical evidence to better inform treatment guidelines.
Clinical Outcomes and Risk Factors for Tunneled Hemodialysis Catheter-Related Bloodstream Infections
Authors: Martin Kylie , Lorenzo Yves S Poy , Leung Po Yee Mia , Chung Sheri , O’flaherty Emmet , Barker Nuala , Ierino Francesco
Published: April 2020

Diabetes and left internal jugular vein insertion site were significantly associated with increased risk of a catheter-related bloodstream infection from a tunneled hemodialysis catheter. Ex-smoker status was significantly associated with reduced risk.
Striatal Dopamine and Reward Prediction Error Signaling in Unmedicated Schizophrenia Patients
Authors: Katthagen Teresa , Kaminski Jakob , Heinz Andreas , Buchert Ralph , Schlagenhauf Florian
Published: April 2020

Increased striatal dopamine synthesis capacity has consistently been reported in patients with schizophrenia. However, the mechanism translating this into behavior and symptoms remains unclear. It has been proposed that heightened striatal dopamine may blunt dopaminergic reward prediction error signaling during reinforcement learning. In this study, we investigated striatal dopamine synthesis capacity, reward prediction errors, and their association in unmedicated schizophrenia patients (n = 19) and healthy controls (n = 23). They took part in FDOPA-PET and underwent functional magnetic resonance imaging (fMRI) scanning, where they performed a reversal-learning paradigm. The groups were compared regarding dopamine synthesis capacity (Kicer), fMRI neural prediction error signals, and the correlation of both. Patients did not differ from controls with respect to striatal Kicer. Taking into account, comorbid alcohol abuse revealed that patients without such abuse showed elevated Kicer in the associative striatum, while those with abuse did not differ from controls. Comparing all patients to controls, patients performed worse during reversal learning and displayed reduced prediction error signaling in the ventral striatum. In controls, Kicer in the limbic striatum correlated with higher reward prediction error signaling, while there was no significant association in patients. Kicer in the associative striatum correlated with higher positive symptoms and blunted reward prediction error signaling was associated with negative symptoms. Our results suggest a dissociation between striatal subregions and symptom domains, with elevated dopamine synthesis capacity in the associative striatum contributing to positive symptoms while blunted prediction error signaling in the ventral striatum related to negative symptoms.
Severe Necrotizing Pneumonia in Children: A Challenge to Intensive Care Specialist
Authors: Sharma Pradeep Kumar , Vinayak Nikhil , Aggarwal Girraj K , Srivastava R D , Aggarwal Pradeep Kumar , Kushwaha Anand Singh
Published: April 2020

Objective

Necrotizing pneumonia (NP) is recently recognized as a complication of pneumonia. The data on NP are scant from developing world and we aimed to describe the characteristic features of NP in our children.

Study design

Single center retrospective cohort analysis.

Patient selection

Institutional database of children treated for pneumonia between September 2014 and May 2018 was searched to identify children with NP.

Methods

The demographic characteristics, laboratory results, and clinical information were recorded for patients selected as NP and analyzed.

Results

In total, 10 patients (3.7%) of NP were identified out of 272 patients with pneumonia. Median age was 3 years (range: 3 months to 12years). All cases had severe respiratory distress and 70% required mechanical ventilation and inotropic support. The causative pathogens were identified in 6/10 children (60%) with Staphylococcus aureus being most common (4/10). Pleural effusion and pneumothorax were seen in six cases. Four cases had bilateral pleural effusion and three had bilateral pneumothorax. Intercostal drainage (ICD) was placed in 70% and bilateral ICD was placed in 40% cases. Bronchopleural fistula (BPF) developed in two cases and one had bilateral BPF. Median [inter quartile range] ICD days and hospital stay were 9 (6–14) and 13.5 (7.5–18.5) days, respectively. Mean (±SD) total antibiotic (in hospital plus outpatient) days were 28.8 ± 9.6 days. Four cases had airway hemorrhage and in three cases this was massive and fatal.

Conclusion

NP is a relatively rare but severe complication of pneumonia distinct from pediatric acute respiratory distress, pleural effusion and empyema. Airway hemorrhage is the most fatal complication.
Cybersecurity regulation in the financial sector: prospects of legal harmonization in the European Union and beyond
Authors: Didenko Anton N
Published: April 2020

Over the past several years, the cybersecurity regulatory landscape has undergone unprecedented change. Bespoke cybersecurity laws and regulations have replaced pre-existing general risk management and business continuity rules in a number of jurisdictions, including the European Union, Hong Kong, Russia, the USA, and Singapore. Cybersecurity has also become the focus of international rules and recommendations adopted by numerous international organizations. The financial sector lies at the centre of the new regulatory initiatives—which, in the absence of an agreed international approach, vary substantially across jurisdictions. This article analyses these emerging legal frameworks by (i) conducting a comparative study of the novel cybersecurity regulations in finance; (ii) identifying the common features of such frameworks; and (iii) assessing the prospect of their harmonization at an international level. It argues that international harmonization in this area is necessary to overcome the underlying regulatory challenges and outlines the scope of rules amenable, first, to initial (de minimis) and, second, subsequent (more expansive) harmonization. The article concludes with a list of main upcoming challenges in designing and harmonizing cybersecurity regulations in finance and practical recommendations for overcoming them.
Measuring Farm Labor: Survey Experimental Evidence from Ghana
Authors: Gaddis Isis , Oseni Gbemisola , Palacios-Lopez Amparo , Pieters Janneke
Published: April 2020

This study examines recall bias in farm labor through a randomized survey experiment in Ghana, comparing farm labor estimates from an end-of-season recall survey with data collected weekly throughout the agricultural season. Recall households report 10 percent more farm labor per person-plot, which can be explained by recall households’ underreporting of “marginal” plots and household workers. This “selective” omission by recall households, denoted as listing bias, alters the composition of plots and workers across treatment arms and inflates average farm labor hours per person-plot in the recall group. Since listing bias, in this setting, dominates other forms of recall bias at higher levels of aggregation (i.e., when farm labor per person-plot is summed at the plot, person, or household level), farm labor productivity is overestimated for recall households. Consistent with the notion that recall bias is linked to the cognitive burden of reporting on past events, there is no recall bias among more educated households.
Rapidin silicodesign of antibodies targeting SARS-CoV-2 using machine learning and supercomputing
Authors: Desautels Thomas , Zemla Adam , Lau Edmond , Franco Magdalena , Faissol Daniel
Published: April 2020

Rapidly responding to novel pathogens, such as SARS-CoV-2, represents an extremely challenging and complex endeavor. Numerous promising therapeutic and vaccine research efforts to mitigate the catastrophic effects of COVID-19 pandemic are underway, yet an efficacious countermeasure is still not available. To support these global research efforts, we have used a novel computational pipeline combining machine learning, bioinformatics, and supercomputing to predict antibody structures capable of targeting the SARS-CoV-2 receptor binding domain (RBD). In 22 days, using just the SARS-CoV-2 sequence and previously published neutralizing antibody structures for SARS-CoV-1, we generated 20 initial antibody sequences predicted to target the SARS-CoV-2 RBD. As a first step in this process, we predicted (and publicly released) structures of the SARS-CoV-2 spike protein using homology-based structural modeling. The predicted structures proved to be accurate within the targeted RBD region when compared to experimentally derived structures published weeks later. Next we used ourin silicodesign platform to iteratively propose mutations to SARS-CoV-1 neutralizing antibodies (known not to bind SARS-Cov-2) to enable and optimize binding within the RBD of SARS-CoV-2. Starting from a calculated baseline free energy of −48.1 kcal/mol (± 8.3), our 20 selected first round antibody structures are predicted to have improved interaction with the SARS-CoV-2 RBD with free energies as low as −82.0 kcal/mole. The baseline SARS-CoV-1 antibody in complex with the SARS-CoV-1 RBD has a calculated interaction energy of −52.2 kcal/mole and neutralizes the virus by preventing it from binding and entering the human ACE2 receptor. These results suggest that our predicted antibody mutants may bind the SARS-CoV-2 RBD and potentially neutralize the virus. Additionally, our selected antibody mutants score well according to multiple antibody developability metrics. These antibody designs are being expressed and experimentally tested for binding to COVID-19 viral proteins, which will provide invaluable feedback to further improve the machine learning–driven designs. This technical report is a high-level description of that effort; the Supplementary Materials includes the homology-based structural models we developed and 178,856in silicofree energy calculations for 89,263 mutant antibodies derived from known SARS-CoV-1 neutralizing antibodies.
On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2
Authors: Corrêa Giron Carolina , Laaksonen Aatto , Barroso da Silva Fernando L.
Published: April 2020

A new betacoronavirus named SARS-CoV-2 has emerged as a new threat to global health and economy. A promising target for both diagnosis and therapeutics treatments of the new disease named COVID-19 is the coronavirus (CoV) spike (S) glycoprotein. By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1. Based on physical chemical analysis and free energies estimates, we can shed some light on the involved molecular recognition processes, their clinical aspects, the implications for drug developments, and suggest structural modifications on the CR3022 antibody that would improve its binding affinities for SARS-CoV-2 and contribute to address the ongoing international health crisis.
The Framework for the Prediction of the Critical Turning Period for Outbreak of COVID-19 Spread in China based on the iSEIR Model1
Authors: Yuan George Xianzhi , Di Lan , Gu Yudi , Qian Guoqi , Qian Xiaosong
Published: April 2020

The goal of this study is to establish a general framework for predicting the so-called critical “Turning Period” in an infectious disease epidemic such as the COVID-19 outbreak in China early this year. This framework enabled a timely prediction of the turning period when applied to Wuhan COVID-19 epidemic and informed the relevant authority for taking appropriate and timely actions to control the epidemic. It is expected to provide insightful information on turning period for the world’s current battle against the COVID-19 pandemic.

The underlying mathematical model in our framework is the individual Susceptible-Exposed-Infective-Removed (iSEIR) model, which is a set of differential equations extending the classic SEIR model. We used the observed daily cases of COVID-19 in Wuhan from February 6 to 10, 2020 as the input to the iSEIR model and were able to generate the trajectory of COVID-19 cases dynamics for the following days at midnight of February 10 based on the updated model, from which we predicted that the turning period of CIVID-19 outbreak in Wuhan would arrive within one week after February 14. This prediction turned to be timely and accurate, providing adequate time for the government, hospitals, essential industry sectors and services to meet peak demands and to prepare aftermath planning.

Our study also supports the observed effectiveness on flatting the epidemic curve by decisively imposing the “Lockdown and Isolation Control Program” in Wuhan since January 23, 2020. The Wuhan experience provides an exemplary lesson for the whole world to learn in combating COVID-19.
The Implementation Research Logic Model: A Method for Planning, Executing, Reporting, and Synthesizing Implementation Projects
Authors: Smith Justin D. , Li Dennis H. , Rafferty Miriam R.
Published: April 2020

Background

Numerous models, frameworks, and theories exist for specific aspects of implementation research, including for determinants, strategies, and outcomes. However, implementation research projects often fail to provide a coherent rationale or justification for how these aspects are selected and tested in relation to one another. Despite this need to better specify the conceptual linkages between the core elements involved in projects, few tools or methods have been developed to aid in this task. The Implementation Research Logic Model (IRLM) was created for this purpose and to enhance the rigor and transparency of describing the often-complex processes of improving the adoption of evidence-based practices in healthcare delivery systems.

Methods

The IRLM structure and guiding principles were developed through a series of preliminary activities with multiple investigators representing diverse implementation research projects in terms of contexts, research designs, and implementation strategies being evaluated. The utility of the IRLM was evaluated in the course of a two-day training to over 130 implementation researchers and healthcare delivery system partners.

Results

Preliminary work with the IRLM produced a core structure and multiple variations for common implementation research designs and situations, as well as guiding principles and suggestions for use. Results of the survey indicated high utility of the IRLM for multiple purposes, such as improving rigor and reproducibility of projects; serving as a “roadmap” for how the project is to be carried out; clearly reporting and specifying how the project is to be conducted; and understanding the connections between determinants, strategies, mechanisms, and outcomes for their project.

Conclusions

The IRLM is a semi-structured, principles-guided tool designed to improve the specification, rigor, reproducibility, and testable causal pathways involved in implementation research projects. The IRLM can also aid implementation researchers and implementation partners in the planning and execution of practice change initiatives. Adaptation and refinement of the IRLM is ongoing, as is the development of resources for use and applications to diverse projects, to address the challenges of this complex scientific field.
Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases
Authors: Zhou Lulin , Niu Zubiao , Jiang Xiaoyi , Zhang Zhengrong , Zheng You , Wang Zhongyi , Zhu Yichao , Gao Lihua , Huang Hongyan , Wang Xiaoning , Sun Qiang
Published: April 2020

Single-cell RNA profiling of ACE2, the SARS-CoV-2 receptor, had proposed multiple tissue cells as the potential targets of SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic. However, most were not echoed by the patients’ clinical manifestations, largely due to the lack of protein expression information of ACE2 and co-factors. Here, we incorporated the protein information to analyse the expression of ACE2, together with TMPRSS2 and Furin, two proteases assisting SARS-CoV-2 infection, at single cell levelin situ, which we called protein-proofed single-cell RNA (pscRNA) profiling. Systemic analysis across 36 tissues revealed a rank list of candidate cells potentially vulnerable to SARS-CoV-2. The top targets are lung AT2 cells and macrophages, then cardiomyocytes and adrenal gland stromal cells, followed by stromal cells in testis, ovary and thyroid. Whereas, the polarized kidney proximal tubule cells, liver cholangiocytes and intestinal enterocytes are less likely to be the primary SARS-CoV-2 targets as ACE2 localizes at the apical region of cells, where the viruses may not readily reach. Actually, the stomach may constitute a physical barrier against SARS-CoV-2 as the acidic environment in normal stomach (pH < 2.0) could completely inactivate SARS-CoV-2 pseudo-viruses. These findings are in concert with the clinical characteristics of prominent lung symptoms, frequent heart injury, and uncommon intestinal symptoms and acute kidney injury. Together, we provide a comprehensive view on the potential SARS-CoV-2 targets by pscRNA profiling, and propose that, in addition to acute respiratory distress syndrome, attentions should also be paid to the potential injuries in cardiovascular, endocrine and reproductive systems during the treatment of COVID-19 patients.
The unseen and pervasive threat of COVID-19 throughout the US
Authors: Javan Emily , Fox Spencer J. , Meyers Lauren Ancel
Published: April 2020

For each US county, we calculated the probability of an ongoing COVID-19 epidemic that may not yet be apparent. Based on confirmed cases as of April 15, 2020, COVID-19 is likely spreading in 86% of counties containing 97% of US population. Proactive measures before two cases are confirmed are prudent.
Estimation of the percentages of asymptomatic patients and undiagnosed patients of the novel coronavirus (SARS-CoV-2) infection in Hokkaido, Japan by using birth-death process with recursive full tracing
Authors: Tanaka Takuma , Yamaguchi Takayuki , Sakamoto Yohei
Published: April 2020

Estimating the percentages of undiagnosed and asymptomatic patients is essential for controlling the outbreak of SARS-CoV-2, and for assessing any strategy for controlling the disease. In this paper, we propose a novel analysis based on the birth-death process with recursive full tracing. We estimated the numbers of undiagnosed symptomatic patients and total infected individuals per diagnosed patient before and after the declaration of the state of emergency in Hokkaido, Japan. The median of the estimated number of undiagnosed symptomatic patients per diagnosed patient decreased from 1.9 to 0.77 after the declaration, and the median of the estimated number of total infected individuals per diagnosed patient decreased from 4.7 to 2.4. We will discuss the limitations and possible expansions of the model.
The effectiveness of non-pharmaceutical interventions in containing epidemics: a rapid review of the literature and quantitative assessment
Authors: Cheatley Jane , Vuik Sabine , Devaux Marion , Scarpetta Stefano , Pearson Mark , Colombo Francesca , Cecchini Michele
Published: April 2020

The number of confirmed COVID-19 cases has rapidly increased since discovery of the disease in December 2019. In the absence of medical countermeasures to stop the spread of the disease (i.e. vaccines), countries have responded by implementing a suite of non-pharmaceutical interventions (NPIs) to contain and mitigate COVID-19. Individual NPIs range in intensity (e.g. from lockdown to public health campaigns on personal hygiene), as does their impact on reducing disease transmission. This study uses a rapid review approach and investigates evidence from previous epidemic outbreaks to provide a quantitative assessment of the effectiveness of key NPIs used by countries to combat the COVID-19 pandemic. Results from the study are designed to help countries enhance their policy response as well as inform transition strategies by identifying which policies should be relaxed and which should not.
Making sense of the Global Coronavirus Data: The role of testing rates in understanding the pandemic and our exit strategy
Authors: Potluri Rahul , Lavu Deepthi
Published: April 2020

The Coronavirus disease 2019(COVID-19) outbreak has caused havoc across the world. Subsequently, research on COVID-19 has focused on number of cases and deaths and predicted projections have focused on these parameters. We propose that the number of tests performed is a very important denominator in understanding the COVID-19 data. We analysed the number of diagnostic tests performed in proportion to the number of cases and subsequently deaths across different countries and projected pandemic outcomes.

We obtained real time COVID-19 data from the reference website Worldometer at 0900 BST on Saturday 4th April, 2020 and collated the information obtained on the top 50 countries with the highest number of COVID 19 cases. We analysed this data according to the number of tests performed as the main denominator. Country wise population level pandemic projections were extrapolated utilising three models - 1) inherent case per test and death per test rates at the time of obtaining the data (4/4/2020 0900 BST) for each country; 2) rates adjusted according to the countries who conducted at least 100000 tests and 3) rates adjusted according to South Korea.

We showed that testing rates impact on the number of cases and deaths and ultimately on future projections for the pandemic across different countries. We found that countries with the highest testing rates per population have the lowest death rates and give us an early indication of an eventual COVID-19 mortality rate. It is only by continued testing on a large scale that will enable us to know if the increasing number of patients who are seriously unwell in hospitals across the world are the tip of the iceberg or not. Accordingly, obtaining this information through a rapid increase in testing globally is the only way which will enable us to exit the COVID-19 pandemic and reduce economic and social instability.
Characterizing relevant microRNA editing sites in Parkinson’s disease
Authors: Lu Chenyu , Ren Shuchao , Zhao Zhigang , Wu Xingwang , Suo Angbaji , Zhou Nan , Yang Jun , Wu Shuai , Li Tianqing , Peng Chao , Zheng Yun
Published: April 2020

MicroRNAs (miRNAs) are extensively edited in human brains. However, the functional relevance of miRNA editome is largely unknown in Parkinson’s disease (PD). By analyzed small RNA sequencing profiles of brain tissues of 43 PD patients and 88 normal controls, we totally identified 421 miRNA editing sites with significantly different editing levels in prefrontal cortices of PD patients (PD-PC). A-to-I edited miR-497-5p has significantly higher expression levels in PD-PC compared to normal controls and directly represses OPA1 and VAPB, which potentially contributes to the progressive neurodegeneration of PD patients. These results provide new insights into mechanistic understanding, novel diagnostic and therapeutic clues of PD.
Hypertension in patients hospitalized with COVID-19 in Wuhan, China: A single-center retrospective observational study
Authors: Zeng Zhenhua , Sha Tong , Zhang Yuan , Wu Feng , Hu Hongbin , Li Haijun , Han Jiafa , Song Wenhong , Huang Qiaobing , Chen Zhongqing
Published: April 2020

Objectives

It is unclear whether patients with hypertension are more likely to be infected with SARS-COV-2 than the general population and whether there is a difference in the severity of COVID-19 pneumonia in patients who have taken ACEI/ARB drugs to lower blood pressure compared to those who have not.

Methods

This observational study included data from all patients with clinically confirmed COVID-19 who were admitted to the Hankou Hospital, Wuhan, China between January 5 and March 8, 2020. Data were extracted from clinical and laboratory records. Follow-up was cutoff on March 8, 2020.

Results

A total of 274 patients, 75 with hypertension and 199 without hypertension, were included in the analysis. Patients with hypertension were older and were more likely to have pre-existing comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease than patients without hypertension. Moreover, patients with hypertension tended to have higher positive COVID-19 PCR detection rates. Patients with hypertension who had previously taken ACEI/ARB drugs for antihypertensive treatment have an increased tendency to develop severe pneumonia after infection with SARS-COV-2 (P = 0.064).

Conclusions

COVID-19 patients with hypertension were significantly older and were more likely to have underlying comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease. Patients with hypertension who had taken ACEI/ARB drugs for antihypertensive treatment have an increased tendency to develop severe pneumonia after infection with SARS-COV-2. In future studies, a larger sample size and multi-center clinical data will be needed to support our conclusions.
The need of health policy perspective to protect Healthcare Workers during COVID-19 pandemic. A GRADE rapid review on the N95 respirators effectiveness
Authors: Iannone Primiano , Castellini Greta , Coclite Daniela , Napoletano Antonello , Fauci Alice , Iacorossi Laura , D’Angelo Daniela , Renzi Cristina , La Torre Giuseppe , Mastroianni Claudio M. , Gianola Silvia
Published: April 2020

Protecting Health Care Workers (HCWs) during routine care of suspected or confirmed COVID-19 patients is of paramount importance to halt the SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) pandemic. The WHO, ECDC and CDC have issued conflicting guidelines on the use of respiratory filters (N95) by HCWs. We searched PubMed, Embase and The Cochrane Library from the inception to March 21, 2020 to identify randomized controlled trials (RCTs) comparing N95 respirators versus surgical masks for prevention of COVID-19 or any other respiratory infection among HCWs. The grading of recommendations, assessment, development, and evaluation (GRADE) was used to evaluate the quality of evidence. Four RCTs involving 8736 HCWs were included. We did not find any trial specifically on prevention of COVID-19. However, wearing N95 respirators can prevent 73 more (95% CI 46-91) clinical respiratory infections per 1000 HCWs compared to surgical masks (2 RCTs; 2594 patients; low quality of evidence). A protective effect of N95 respirators in laboratory-confirmed bacterial colonization (RR= 0.41; 95%CI 0.28-0.61) was also found. A trend in favour of N95 respirators was observed in preventing laboratory-confirmed respiratory viral infections, laboratory-confirmed respiratory infection, and influenza like illness. We found no direct high quality evidence on whether N95 respirators are better than surgical masks for HCWs protection from SARS-CoV-2. However, low quality evidence suggests that N95 respirators protect HCWs from clinical respiratory infections. This finding should be contemplated to decide the best strategy to support the resilience of healthcare systems facing the potentially catastrophic SARS-CoV-2 pandemic.
Key to successful treatment of COVID-19: accurate identification of severe risks and early intervention of disease progression
Authors: Chen Meizhu , Tu Changli , Tan Cuiyan , Zheng Xiaobin , Wang Xiaohua , Wu Jian , Huang Yiying , Wang Zhenguo , Yan Yan , Li Zhonghe , Shan Hong , Liu Jing , Huang Jin
Published: April 2020

Background

COVID-19 is a new and highly contagious respiratory disease that has caused global spread, high case fatality rate in severe patients, and a huge medical burden due to invasive mechanical ventilation. The current diagnosis and treatment guidelines are still need to be improved, and more excellent clinical experience is needed to provide reference.

Methods

We analyzed and summarized clinical data of 97 confirmed COVID-19 adult patients (including 26 severe cases) admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from January 17, 2020 to March 10, 2020, included laboratory examination results, imaging findings, treatment effect, prognosis, etc, in order to put forward prediction index of severe COVID-19 patients, principles of early intervention and methylprednisolone usages in COVID-19 patients.

Results

Hypoxemia, hyperlactic acid, hypoproteinemia, and hypokalemia were prevalent in COVID-19 patients. The significant low lymphocyte count, hypoproteinemia, hypokalemia, the persistent or worsen high CRP, high D-dimer, and high BNP, and the occurrence of hemoptysis and novel coronavirus (SARS-CoV-2) viremia were important indicators for early diagnosis and prediction of severe disease progression.

Characteristic images of lung CT had a clear change in COVID-19, Ground-glass opacity (GGO) and high-density linear combinations may indicate different pathological changes. Rapid lobular progression of GGO suggests the possibility of severe disease.

Basic principles of early intervention treatment of COVID-19: on the premise of no effective antiviral drugs, treatment is based on supportive and symptomatic therapy (albumin supplementation, supplement of potassium, supplement blood plasma, etc.) in order to maintain the stability of the intracellular environment and adequately reactivate body immunity to clean up SARS-CoV-2.

According to severity, oxygenation index, body weight, age, underlying diseases, appropriate amount methylprednisolone application on severe/critical COVID-19 patients on demand, improved blood oxygen and reduced the utilization rate of invasive mechanical ventilation, case fatality rate and medical burden significantly. The most common indications for invasive mechanical ventilation should be strictly control in critical COVID-19 patients.

Conclusions

Accurate and timely identification of clinical features in severe risks, and early and appropriate intervention can block disease progression. 2. Appropriate dose of methylprednisolone can effectively avoid invasive mechanical ventilation and reduce case fatality rate in critical COVID-19 patients.
Multi-route respiratory infection: when a transmission route may dominate
Authors: Gao Caroline X. , Li Yuguo , Wei Jianjian , Cotton Sue , Hamilton Matthew , Wang Lei , Cowling Benjamin J.
Published: April 2020

The exact transmission route of many respiratory infectious diseases remains a subject for debate to date. The relative contribution ratio of each transmission route is largely undetermined, which is affected by environmental conditions, human behavior, the host and the microorganism. In this study, a detailed mathematical model is developed to investigate the relative contributions of different transmission routes to a multi-route transmitted respiratory infection. It is illustrated that all transmission routes can dominate the total transmission risk under different scenarios. Influential parameters considered include dose-response rate of different routes, droplet governing size that determines virus content in droplets, exposure distance, and virus dose transported to the hand of infector. Our multi-route transmission model provides a comprehensive but straightforward method to evaluate the transmission efficiency of different transmission routes of respiratory diseases and provides a basis for predicting the impact of individual level intervention methods such as increasing close-contact distance and wearing protective masks. (Word count: 153)

Highlights

A multi-route transmission model is developed by considering evaporation and motion of respiratory droplets with the respiratory jet and consequent exposure of the susceptible.

We have illustrated that each transmission route may dominate during the influenza transmission, and the influential factors are revealed.

The short-range airborne route and infection caused by direct inhalation of medium droplets are highlighted.
Analysing and comparing the COVID-19 data: The closed cases of Hubei and South Korea, the dark March in Europe, the beginning of the outbreak in South America
Authors: De Leo Stefano , Maia Gabriel G. , Solidoro Leonardo
Published: April 2020

The present work is a statistical analysis of the COVID-19 pandemic. As the number of cases worldwide overtakes one million, data reveals closed outbreaks in Hubei and South Korea, with a new slight increase in the number of infected people in the latter. Both of these countries have reached a plateau in the number of Total Confirmed Cases per Million (TCCpM) residents, suggesting a trend to be followed by other affected regions. Using Hubei’s data as a basis of analysis, we have studied the spreading rate of COVID-19 and modelled the epidemic center for 10 European countries. We have also given the final TCCpM curves for Italy and Lombardia. The introduction of the α-factor allows us to analyse the different stages of the outbreak, compare the European countries amongst each other, and, finally, to confront the initial phase of the disease between Europe and South America.

Methods

By dividing the TCCpM curves in multiple sections spanning short time frames we were able to fit each section to a linear model. By pairing then the angular coefficient (α factor) of each section to the total number of confirmed infections at the center of the corresponding time interval, we have analysed how the spreading rate of Covid-19 changes as more people are infected. Also, by modelling the TCCpM curves with an asymmetrical time integral of a Normal Distribution, we were able to study, by fitting progressively larger data ensembles, how the fitting parameters change as more data becomes available.

Findings

The data analysis shows that the spreading rate of COVID-19 increases similarly for all countries in its early stage, but changes as the number of TCCpM in each country grows. Regarding the modelling of the TCCpM curves, we have found that the fitting parameters oscillate with time before reaching constant values. The estimation of such values allows the determination of better parameters for the model, which in turn leads to more trustworthy forecasts on the pandemic development.

Interpretation

The analysis of the oscillating fitting parameters allows an early prediction of the TCC, epidemic center and standard deviation of the outbreak. The α factor and the recovered over confirmed cases ratio can be used to understand the pandemic development in each country and to compare the protective measures taken by local authorities and their impact on the spreading of the disease.

Funding

CNPq (grant number 2018/303911) and Fapesp (grant numebr 2019/06382-9).
Alternative Qualitative Fit Testing Method for N95 Equivalent Respirators in the Setting of Resource Scarcity at the George Washington University
Authors: Provenzano Destie , Rao Yuan James , Mitic Konstantin , Obaid Sofian N. , Berger Jeffrey , Goyal Sharad , Loew Murray H.
Published: April 2020

The 2019 Novel Coronavirus (COVID-19) has caused an acute shortage of personal protective equipment (PPE) globally as well as shortage in the ability to test PPE such as respirator fit testing. This limits not only the ability to fit PPE to medical practitioners, but also the ability to rapidly prototype and produce alternative sources of PPE as it is difficult to validate fit. At the George Washington University, we evaluated an easily sourced method of qualitative fit testing using a nebulizer or “atomizer” and a sodium saccharin solution in water. If aerosolized saccharin entered candidate masks due to poor fit or inadequate filtration, then a sweet taste was detected in the mouth of the user. This method was tested against previously fit tested Milwaukee N95 and 3D Printed Reusable N95 Respirator as a positive control. A Chinese sourced KN95, cotton cloth material, and surgical mask were tested as other masks of interest. Sensitivity testing was done with no mask prior to fit test. A sweet taste was detected for both the surgical mask and cotton cloth, demonstrating a lack of seal. However, there was no sweet taste detected for the Milwaukee N95, 3D Printed Reusable N95 Respirator, or Chinese KN95. These results demonstrate this could be a valuable methodology for rapid prototyping, evaluation, and validation of fit in a non-clinical environment for use in creation of PPE. This method should be not be used without confirmation in a formal qualitative or quantitative fit test but can be used to preserve those resources until developers are confident that potential new N95 comparable respirators will pass. We strongly suggest validation of masks and respirators with Occupational Safety and Health Administration (OSHA) approved fit testing prior to use in a clinical environment.