bluuebunny/crossref_metadata_2025_split huggingface dataset:
RPA-Based Method For The Detection Of SARS-COV2
Authors: Nassir Angus A. , Baptiste Mazarati Jean , Mwikarago Ivan , Habimana Majidi R. , Ndinkabandi Janvier , Murangwa Anthere , Nyatanyi Thierry , Muvunyi Claude Mambo , Nsanzimana Sabin , Leon Mutesa , Musanabaganwa Clarisse 
Published: September 2020

AbstractBackgroundCoronavirus disease 2019 (COVID-19) is a highly infectious disease with significant mortality, morbidity, and far-reaching economic and social disruptions. Testing is key in the fight against COVID-19 disease. The gold standard for COVID-19 testing is the reverse transcription polymerase chain reaction (RT-PCR) test. RT-PCR requires highly specialized, expensive, and advanced bulky equipment that is difficult to use in the field or in a point of care setting. There is need for a simpler, inexpensive, convenient, portable and accurate test. Our aims were to: (i) design primer-probe pairs for use in isothermal amplification of the S1, ORF3 and ORF8 regions of the SARS-CoV2 virus; (ii) optimize the recombinase polymerase amplification (RPA) assay for the isothermal amplification of the named SARS-COV2 regions; (iii) detect amplification products on a lateral flow device. and (ii) perform a pilot field validation of RPA on RNA extracted from nasopharyngeal swabs.ResultsAssay validation was done at the National Reference Lab (NRL) at the Rwanda Biomedical Center (RBC) in Rwanda. Results were compared to an established, WHO-approved rRT-PCR laboratory protocol. The assay provides a faster and cheaper alternative to rRT-PCR with 100% sensitivity, 93% specificity, and positive and negative predictive agreements of 100% and 93% respectively.ConclusionTo the best of our knowledge, this is the first in-field and comparative laboratory validation of RPA for COVID-19 disease in low resource settings. Further standardization will be required for deployment of the RPA assay in field settings.
Epidemiology of SARS-CoV-2 infection in Karnataka State, South India: Transmission dynamics of symptomatic vs. asymptomatic infections
Authors: Kumar Narendra , Hameed Shafeeq K Shahul , Babu Girdhara R , Venkataswamy Manjunatha M , Dinesh Prameela , Kumar Prakash BG , John Daisy A. , Desai Anita , Ravi Vasanthapuram 
Published: September 2020

AbstractBackgroundIn this report, we describe the epidemiology of SARS-CoV-2 infection, specifically examining how the symptomatic persons drove the transmission in the state of Karnataka, India, during the lockdown phase.MethodsThe study included all the cases reported from March 8 to May 31, 2020 in the state. Any person with history of international or domestic travel from high burden states, those presenting with Influenza-like or Severe Acute Respiratory Illness and high-risk contacts of COVID19 cases, who were SARS-CoV-2 RT-PCR positive were included. Detailed analysis based on contact tracing data available from line-list of the state surveillance unit was performed using cluster analysis software package.FindingsAmongst the 3404 COVID-19 positive cases, 3096 (91%) were asymptomatic while 308 (9%) were symptomatic. Majority of the asymptomatic cases were in the age range of 16-50 years while symptomatic cases were between 31-65 years. Most of those affected were males. Cluster analysis of 822 cases indicated that the secondary attack rate, size of the cluster (dispersion) and occurrence of overt clinical illness is significantly higher when the index case in a cluster was symptomatic compared to an asymptomatic.InterpretationOur findings indicate that both asymptomatic and symptomatic SARS-CoV-2 cases transmit the infection; however, the main driving force behind the spread of infection within the state was significantly higher from symptomatic cases. This has major implications for policies related to testing. Active search for symptomatic cases, subjecting them to testing and treatment should be prioritized for containing the spread of COVID-19.FundingIntermediate Fellowship, Wellcome Trust-DBT India Alliance to Giridhara R Babu, Grant number: IA/CPHI/14/1/501499.
The impact of vital signs on the death of patients with new coronavirus pneumonia: A systematic review and meta-analysis
Authors: Du Meixia , Zhao Jie , Yin Xiaochun , Zhang Nadi , Zheng Guisen 
Published: September 2020

AbstractBackgroundAssessing the impact of vital signs (blood pressure, body temperature, heart rate, respiratory rate, and oxygen saturation) on the death of patients with new coronavirus pneumonia would provide a simple and convenient method for the monitoring of subsequent illness, and therefore, in some degree reduce treatment costs and increase the cure rate clinically.MethodsSix databases were retrieved. The software R 3.6.2 was used for meta-analysis of the included literature.Results12 studies were included, which comprise 8996 patients affected with COVID-19 infection. The meta-analysis study found that blood pressure (MAP, SBP and DBP), heart rate, respiration rate and SpO2 are the risk factors for disease progression in patients with COVID-19. Among them, the increase in MAP and the decrease in SpO2 have the greatest impact on the death of patients with COVID-19 [MAP: MD = 5.66, 95% CI (0.34, 10.98), SpO2: MD = −5.87, 95% CI (−9.17, −2.57), P = 0.0005]. However, comparing the body temperature of the death group and the survival group found that the body temperature was not statistically significant between the two groups [body temperature: MD = 0.21, 95% CI (−0.01, 0.43), P = 0.0661].ConclusionThe increase in MAP, heart rate and respiratory rate, as well as the decrease in SBP, DBP and SpO2 are all independent risk factors for death in patients with COVID-19. These factors are simple and easy to monitor, and individualized treatment can be given to patients in time, reducing the mortality rate and improving treatment efficiency.
Anterior Knee Pain Risk Differs Between Male and Female Military Tactical Athletes
Authors: Glaviano Neal R. , Boling Michelle C. , Fraser John J. 
Published: September 2020

ABSTRACTBackgroundAnterior knee pain (AKP) is commonly diagnosed in military members and is a threat to operational readiness. AKP includes a range of conditions, with localized pain around the patella being a frequent location of pain and disability. Mechanical overuse is one suggested etiology for many of these conditions, suggesting occupational demands in the military may influence AKP frequency amongst the service members. Previous research suggests females are at a greater risk for AKP, however, it is unknown how occupation affects AKP risk.Study DesignEpidemiological cohort.Level of EvidenceLevel 2.MethodsThe Defense Medical Epidemiology Database was queried for the number of individuals with ICD-9 diagnosis codes on their initial encounter from 2006 to 2015. Diagnoses were categorized into anterior or retropatellar pain, patellar instability, knee tendinopathy, as well the sum of the three groups which was defined as AKP. Relative risk (RR) and chi-square statistics were calculated in the assessment of sex and occupational category. Regressions were calculated to determine association between service branch, sex, and AKP across time.ResultsFrom 2006-2018, a total of 151, 263 enlisted and 14,335 officer services members were diagnosed with AKP. The incidence rate was 13.2 in enlisted members and 6.2 in in officers. Females were significantly at greater risk of developing AKP compared to males within both the enlisted (relative risk=1.32) and officer (relative risk=2.01) service members. Differences in risk were also noted across military occupation for both enlisted and officer service members, p<.05.ConclusionSex and military occupation were salient factors for AKP risk. Evaluation of training requirements and developing interventions programs across military occupation could serve as a focus for future research aiming to decrease the incidence of chronic knee pain.
Mixed cytomegalovirus genotypes in HIV positive mothers show compartmentalization and distinct patterns of transmission to infants
Authors: Pang Juanita , Slyker Jennifer A. , Roy Sunando , Bryant Josephine , Atkinson Claire , Cudini Juliana , Farquhar Carey , Griffiths Paul , Kiarie James , Morfopoulou Sofia , Roxby Alison C. , Tutil Helena , Williams Rachel , Gantt Soren , Goldstein Richard A. , Breuer Judith 
Published: September 2020

AbstractCytomegalovirus (CMV) is the most congenital infection (cCMVi), and is particularly common among infants born to HIV-infected women. Studies of cCMVi pathogenesis are complicated by the presence of multiple infecting maternal CMV strains, especially in HIV-positive women, and the large, recombinant CMV genome. Using newly-developed tools to reconstruct CMV haplotypes, we demonstrate anatomic CMV compartmentalization in five HIV-infected mothers, and identify the possibility of congenitally-transmitted genotypes in three of their infants. A single CMV strain was transmitted in each congenitally-infected case, and all were closely related to those that predominate in the cognate maternal cervix. Compared to non-transmitted strains, these congenitally-transmitted CMV strains showed statistically significant similarities in 19 genes associated with tissue-tropism and immunomodulation. In all infants, incident superinfections with distinct strains from breast milk were captured during follow-up. The results represent potentially important new insights into the virologic determinants of early CMV infection.
COVID-19 pediatric mortality rates are heterogeneous between countries
Authors: González-García Nadia , Miranda-Lora América Liliana , Garduño-Espinosa Juan , Granados-Riverón Javier T. , Méndez-Galván Jorge Fernando , Nieto-Zermeño Jaime , Castilla-Peón María F 
Published: September 2020

AbstractIntroductionSevere COVID-19 is infrequent in children, with a lethality rate of about 0.08%. This study aims to explore differences in the pediatric mortality rate between countries.MethodsCountries with populations over 5 million that report COVID-19 deaths disaggregated data by quinquennial or decennial age groups were analyzed. Data were extracted from COVID-19 Cases and Deaths by Age Database, national ministries of health, and the World Health Organization.Results23 countries were included in the analysis. Pediatric mortality varied from 0 to 12.1 deaths per million people of the corresponding age group, with the highest rate in Peru. In most countries, deaths were more frequent in the 0-4 years old age group, except for Brazil. The pediatric/ general COVID-19 mortality showed a great variation between countries and ranged from 0 (Republic of Korea) to 10.4% (India). Pediatric and Pediatric/general COVID mortality have a strong correlation with 2018 neonatal mortality (r=0.77, p<0.001 and r= 0.88, p<0.001 respectively), while it has a moderate or absent (r=0.47, p=0.02 and r=0.19, p=0.38, respectively) correlation with COVID-19 mortality in the general population.ConclusionsThere is an important heterogenicity in pediatric COVI-19 mortality between countries that parallels historical neonatal mortality. Neonatal mortality is a known index of the quality of a country’s Health System which points to the importance of social determinants of health in pediatric COVID-19 mortality disparities, an issue which should be further explored.
Investigating the implications of COVID-19 for the rural and remote population of Northern Ontario using a mathematical model
Authors: Savage DW , Fisher A , Choudhury S , Ohle R , Strasser RP , Orkin A , Mago V 
Published: September 2020

AbstractBackgroundCOVID-19 has the potential to disproportionately affect the rural, remote, and Indigenous populations who typically have a worse health status and live in substandard housing, often with overcrowding. Our aim is to investigate the potential effect of COVID-19 on intensive care unit (ICU) resources and mortality in northwestern Ontario.MethodsThis study was conducted in northwestern Ontario which has a population of 230,000. A set of differential equations were used to represent a modified Susceptible-Infectious-Recovered (SIR) model with urban and rural hospital resources (i.e., ICU and hospital beds). Rural patients requiring ICU care flowed into the urban ICU. Sensitivity analyses were used to investigate the effect of poorer health status (i.e., increased hospital admission, ICU admission, and mortality) and overcrowding (i.e., increased contact rate) in the rural population as compared to the urban population. Physical distancing within the urban population was modelled as a decreased contact rate.ResultsAt the highest contact rate, the peak in daily active cases, ICU bed requirements and mortality was higher and occurred earlier than lower contact rates. The urban population with a lower contact rate and baseline health status had a lower predicted prevalence of active cases and lower mortality than the rural population.InterpretationAn increased contact rate and worse health status in the rural population will likely increase the required ICU resources and mortality as compared to the urban population. Rural populations will likely be affected disproportionately more than urban populations.
On Topological Properties of COVID-19: Predicting and Controling Pandemic Risk with Network Statistics
Authors: So Mike K.P. , Chu Amanda M.Y. , Tiwari Agnes , Chan Jacky N.L. 
Published: September 2020

ABSTRACTThe spread of coronavirus disease 2019 (COVID-19) has caused more than 24 million confirmed infected cases and more than 800,000 people died as of 28 August 2020. While it is essential to quantify risk and characterize transmission dynamics in closed populations using Susceptible-Infection-Recovered modeling, the investigation of the effect from worldwide pandemic cannot be neglected. This study proposes a network analysis to assess global pandemic risk by linking 164 countries in pandemic networks, where links between countries were specified by the level of ‘co-movement’ of newly confirmed COVID-19 cases. More countries showing increase in the COVID-19 cases simultaneously will signal the pandemic prevalent over the world. The network density, clustering coefficients, and assortativity in the pandemic networks provide early warning signals of the pandemic in late February 2020. We propose a preparedness pandemic risk score for prediction and a severity risk score for pandemic control. The preparedness risk score contributed by countries in Asia is between 25% to 50% most of the time after February and America contributes close to 50% recently. The high preparedness risk contribution implies the importance of travel restrictions between those countries. The severity risk score of America is greater than 50% after May and even exceeds 75% in July, signifying that the control of COVID-19 is still worrying in America. We can keep track of the pandemic situation in each country using an online dashboard to update the pandemic risk scores and contributions.
The Peak of COVID-19 in India
Authors: Yadav Suryakant , Yadav Pawan Kumar 
Published: September 2020

AbstractIntroductionFollowing the USA, India ranks the second position in the world for COVID-19 cases with the highest number of daily confirmed cases since September 2020. The peak of COVID-19 cases is the most warranted feature for understanding the curvature of COVID-19 cases.AimThis study aims to analyse the growth rates of the daily confirmed cases and to provide an expected count of the peak of daily confirmed cases.DataWe retrieved data from an Application Programming Interface portal https://www.covid19india.org/ which is open access and publicly available.MethodsExponential model was applied to estimate the growth rates of daily confirmed cases. The estimated growth rates were used for calculating the doubling time. The Lotka-Euler method was applied to calculate the effective reproduction rate. SARIMA model was developed for the growth rates to predict daily confirmed cases.ResultsResults show the best fit of the exponential model over the daily confirmed cases. The growth rates estimated from the exponential model shows an unsteady, modest decline. Doubling time shows a linear increase. The effective reproduction rate declined from 3.6 persons in the third week of March 2020 to 1.14 persons at the end of August 2020 and 1.12 persons in the mid-September 2020. The diagnosis of the developed SARIMA model confirmed no trends in the residuals, no outliers, and nearly constant variance. The forecast suggests the peak value of daily confirmed cases would waver around 105,000 counts in the third week of September 2020. The cumulative COVID-19 cases would account for approximately 105 lakhs at the end of December 2020.ConclusionThe exponential model unravels a shift and a modest decline in the growth of daily confirmed cases. The trends in R(t) show analogue with the trends in growth rates of daily confirmed cases. The study shows that the SARIMA model is suitable for projecting daily confirmed cases. The results shed light on the understanding of the trends and epidemiological stage of COVID-19 disease, in the cognisance of the peak.ContributionThis study based on moments of the distribution of the daily confirmed cases of COVID-19 disease unravels the uncertainty about the peak and curvature of COVID-19 disease.Research HighlightsThe exponential model is the best fit over daily confirmed COVID-19 cases.The trends in growth rates of daily confirmed cases show a swift decline during the five-and-a-half months period since April 2020.The effective reproduction rate in India declined from 3.6 persons in the third week of March 2020 to 1.14 persons at the end of August 2020 and 1.12 persons in the mid of September 2020.The forecast reveals that the peak of daily confirmed cases wavers at approximately 105,000 cases since the third week of September 2020.The R(t) value would be equal to one in the first week of December 2020.The cumulative confirmed cases of COVID-19 in India would account to approximately 105 lakhs at the end of December 2020.
Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1 and TIA1
Authors: Vivori Claudia , Papasaikas Panagiotis , Stadhouders Ralph , Di Stefano Bruno , Balaguer Clara Berenguer , Generoso Serena , Mallol Anna , Sardina José Luis , Payer Bernhard , Graf Thomas , Valcárcel Juan 
Published: September 2020

AbstractIn contrast to the extensively studied rewiring of epigenetic and transcriptional programs required for cell reprogramming, the dynamics of post-transcriptional changes and their associated regulatory mechanisms remain poorly understood. Here we have studied the dynamics of alternative splicing (AS) changes occurring during efficient reprogramming of mouse B cells into induced pluripotent stem (iPS) cells. These changes, generally uncoupled from transcriptional regulation, significantly overlapped with splicing programs reported during reprogramming of mouse embryonic fibroblasts (MEFs). Correlation between gene expression of potential regulators and specific clusters of AS changes enabled the identification and subsequent validation of CPSF3 and hnRNP UL1 as facilitators, and TIA1 as repressor of MEFs reprogramming. These RNA-binding proteins control partially overlapping programs of splicing regulation affecting genes involved in developmental and morphogenetic processes. Our results reveal common programs of splicing regulation during reprogramming of different cell types and identify three novel regulators of this process.
The Quorum Sensing Peptide EntF* Promotes Colorectal Cancer Metastasis in Mice: A New Factor in the Microbiome-Host Interaction
Authors: Debunne Nathan , Wynendaele Evelien , Janssens Yorick , De Spiegeleer Anton , Verbeke Frederick , Tack Liesa , Van Welden Sophie , Goossens Evy , Knappe Daniel , Hoffmann Ralf , Van De Wiele Christophe , Laukens Debby , Van Eenoo Peter , Van Immerseel Filip , De Wever Olivier , De Spiegeleer Bart 
Published: September 2020

ABSTRACTBackgroundColorectal cancer, one of the most common malignancies worldwide, is associated with a high mortality rate, mainly caused by metastasis. Comparative metagenome-wide analyses between healthy individuals and cancer patients suggest a role for the human intestinal microbiota. Nevertheless, which microbial molecules are involved in this communication is largely unknown, with current studies mainly focusing on short chain fatty acids and amino acid metabolites as potential mediators. However, quorum sensing peptides are not yet considered in this microbiome-host interaction: theirin vivopresence nor anyin vivohost-effect have been reported.ResultsFor the first time, we showed that a quorum sensing peptide metabolite, EntF* produced by intestinal microbiota (E. faecium), is present in the blood circulation of mice. Moreover, it significantly promotes colorectal cancer metastasisin vivo, with metastatic lesions found in both liver and lung tissues, using an orthotopic mice model evaluating bioluminescence as well as macroscopic and microscopic presence of metastatic tumour nodules.In vitrotests on E-cadherin expression levels thereby indicated that the first, second, sixth and tenth amino acid of EntF* were critical for the epithelial-mesenchymal transition (EMT) effect, responsible for tumour metastasis.ConclusionThis paper adds a new group of molecules, the quorum sensing peptides, as an additional causative factor explaining the microbiome-host interaction. The presence of a selected quorum sensing peptide (metabolite) in the mouse was proven for the first time and itsin vivoeffect on colorectal metastasis was demonstrated. We anticipate ourin vivoresults to be a starting point for broader microbiome-health investigations, not only limited to colorectal cancer metastasis, but also for developing novel bio-therapeutics in other disease areas, giving due attention to the QSP produced by the microbiome.
Cargo receptor-assisted endoplasmic reticulum export of pathogenic α1-antitrypsin polymers
Authors: Ordonez Adriana , Harding Heather P , Marciniak Stefan J , Ron David 
Published: September 2020

AbstractCirculating polymers of alpha1-antitrypsin (α1AT) are chemo-attractant for neutrophils and contribute to inflammation in pulmonary, vascular and adipose tissues. Cellular factors affecting the intracellular itinerary of mutant polymerogenic α1AT remain obscure. Here, we report on an unbiased genome-wide CRISPR/Cas9 screen for regulators of trafficking of the polymerogenic α1ATH334Dvariant. Single guide RNAs targeting genes whose inactivation enhanced accumulation of polymeric α1AT were enriched by iterative construction of CRISPR libraries based on genomic DNA from fixed cells selected for high polymer content by fluorescence-activated cell sorting. This approach bypassed the limitation to conventional enrichment schemes imposed by cell fixation and identified 121 genes involved in polymer retention at false discovery rate < 0.1. From that set of genes, the pathway ‘cargo loading into COPII-coated vesicles’ was overrepresented with 16 significant genes, including two transmembrane cargo receptors, LMAN1 (ERGIG-53) and SURF4.LMAN1andSURF4-disrupted cells displayed a secretion defect extended beyond α1AT monomers to polymers, whose low-level secretion was especially dependent on SURF4 and correlated with SURF4-α1ATH334Dphysical interaction and with enhanced co-localisation of polymeric α1ATH334Dwith the endoplasmic reticulum (ER). These findings suggest that ER cargo receptors co-ordinate intracellular progression of α1AT out of the ER and modulate the accumulation of polymeric α1AT not only by controlling the concentration of precursor monomers but also through a previously-unrecognised role in secretion of the polymers themselves.