bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advance of Novel Coronavirus Registration Clinical Trial
Authors: Song Gao , Cheng Meng Qun , Wei Xian Wen 
Published: March 2020

AbstractBackgroundTo analyze the characteristics and heterogeneity of clinical trials of Novel Coronavirus(COVID-19) registered in the China Clinical Trial Registry (ChiCTR), and provide data bases and information references for clinical treatmentMethodsStatistics of COVID-19 clinical trials registered with ChiCTR as of February 24, 2020 were collected. Descriptive analysis of registration characteristics. The chi-square test is used to compare statistical differences between different study types, intervention methods, study stage, and Primary sponsor.Results232 COVID-19 studies registered at the ChiCTR were collected. The overall number of COVID-19 registrations was increased. Hubei Province, China has the largest number of registrations. There were significant differences between the number of participants(P=0.000), study duration(P=0.008), study assignment(P=0.000), and blind method(P=0.000) for different study types. Significant differences could be seen in the dimensions of multicenter study(P=0.022), of participants numbe(P=0.000), study duration(P=0.000) and study assignment(P=0.001) for the four intervention methods. There were significant differences in study assignment(P=0.043) between the early and late studies. CMT drugs with high research frequency are chloroquine, lopinavir / ritonavir, and I-IFN; BI was Cell therapy, plasma therapy, Thymosin, and M/P-AB.ConclusionsDifferent study design characteristics have led to significant differences in some aspects of the COVID-19 clinical trial. Timely summary analysis can provide more treatment options and evidence for clinical practice.
Elucidating mechanisms of genetic cross-disease associations: an integrative approach implicates protein C as a causal pathway in arterial and venous diseases
Authors: Stacey David , Chen Lingyan , Howson Joanna M. M. , Mason Amy M. , Burgess Stephen , MacDonald Stephen , Langdown Jonathan , McKinney Harriett , Downes Kate , Farahi Neda , Peters James E. , Basu Saonli , Pankow James S. , Pankratz Nathan , Tang Weihong , Sabater-Lleal Maria , de Vries Paul S. , Smith Nicholas L. ,   CHARGE Hemostasis Working Group, Gelinas Amy D. , Schneider Daniel J. , Janjic Nebojsa , Summers Charlotte , Chilvers Edwin R. , Danesh John , Paul Dirk S. 
Published: March 2020

AbstractGenome-wide association studies have identified many individual genetic loci associated with multiple complex traits and common diseases. There are, however, few examples where the molecular basis of such pleiotropy has been elucidated. To address this challenge, we describe an integrative approach, focusing on the p.Ser219Gly (rs867186 A>G) variant in thePROCRgene (encoding the endothelial protein C receptor, EPCR), which has been associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk. In a phenome scan of 12 cardiometabolic diseases and 24 molecular factors, we found thatPROCR-219Gly associated with higher plasma levels of zymogenic and activated protein C as well as coagulation factor VII. Using statistical colocalization and Mendelian randomization analyses, we uncovered shared genetic etiology across activated protein C, factor VII, CAD and VTE, identifying p.S219G as the likely causal variant at the locus. In a recall-by-genotype study of 52 healthy volunteers stratified by p.S219G, we detected 2.5-fold higher soluble EPCR levels and 1.2-fold higher protein C levels in plasma per effect allele, suggesting the allele induces EPCR shedding from the membrane of endothelial cells. Finally, in cell adhesion assays, we found that increasing concentrations of activated protein C, but not soluble EPCR, reduced leukocyte–endothelial cell adhesion, a marker for vascular inflammation. These results support a role for protein C as a causal factor in arterial and venous diseases, suggesting thatPROCR-219Gly protects against CAD through anti-inflammatory mechanisms while it promotes VTE risk through pro-thrombotic mechanisms. Overall, our study illustrates a multi-modal approach that can help reveal molecular underpinnings of cross-disease associations.
COVID-19: Forecasting short term hospital needs in France
Authors: Massonnaud Clément , Roux Jonathan , Crépey Pascal 
Published: March 2020

1AbstractEurope is now considered as the epicenter of the SARS-CoV-2 pandemic, France being among the most impacted country. In France, there is an increasing concern regarding the capacity of the healthcare system to sustain the outbreak, especially regarding intensive care units (ICU). The aim of this study was to estimate the dynamics of the epidemic in France, and to assess its impact on healthcare resources for each French metropolitan Region. We developed a deterministic, age-structured, Susceptible-Exposed-Infectious-Removed (SEIR) model based on catchment areas of each COVID-19 referral hospitals. We performed one month ahead predictions (up to April 14, 2020) for three different scenarios (R0 = 1.5, R0 = 2.25, R0 = 3), where we estimated the daily number of COVID-19 cases, hospitalizations and deaths, the needs in ICU beds per Region and the reaching date of ICU capacity limits. At the national level, the total number of infected cases is expected to range from 22,872 in the best case (R0 = 1.5) to 161,832 in the worst case (R0 = 3), while the total number of deaths would vary from 1,021 to 11,032, respectively. At the regional level, all ICU capacities may be overrun in the worst scenario. Only seven Regions may lack ICU beds in the mild scenario (R0 = 2.25) and only one in the best case. In the three scenarios, Corse may be the first Region to see its ICU capacities overrun. The two other Regions, whose capacity will be overrun shortly after are Grand-Est and Bourgogne-Franche-Comté. Our analysis shows that, even in the best case scenario, the French healthcare system will very soon be overwhelmed. While drastic social distancing measures may temper our results, a massive reorganization leading to an expansion of French ICU capacities seems to be necessary to manage the coming wave of critically affected COVID-19 patients.
DNA methylation differences at birth after conception through assisted reproductive technologies
Authors: Tobi Elmar W. , Almqvist Catarina , Hedman Anna , Andolf Ellika , Holte Jan , Olofsson Jan I. , Wramsby Håkan , Wramsby Margaretha , Pershagen Göran , Heijmans Bastiaan T. , Iliadou Anastasia N. 
Published: March 2020

SummaryThe possible health consequences of assisted reproductive technology (ART) are a topic of intense study. Epigenetic mechanisms, such as changes in DNA methylation (DNAm), come forward from animal studies as a potential mechanism linking ART and health. Here we report on an epigenome-wide association study (EWAS) of DNAm in cord blood of 87 infants conceived with in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI) and 70 who were not. We found no difference in global methylation levels, but identified nineteen CpG dinucleotides (CpGs) associated with ART (effect estimates: 0.5-4.9%). There was no difference between IVF and ICSI and the CpGs map to genes related to brain function/development or the plethora of conditions linked to subfertility. Functional annotation did not point to likely functional consequences. Concluding, ART is associated with DNA methylation differences in cord blood, but these differences are limited in number, effect size and with unknown functional consequences.
Characterisation of sperm piRNAs and their correlation with semen quality traits in swine
Authors: Ablondi M. , Gòdia M. , Rodriguez-Gil J. E. , Sánchez A. , Clop A. 
Published: March 2020

SummaryPiwi-interacting RNAs (piRNAs) are a class of non-coding RNAs which main reported function consists on the silencing of transposable elements and genome stability in mammalian germline. In this study we have identified piRNAs in porcine sperm, using male germline and zygote datasets from human, mice, cow and swine, and evaluated the relation between their abundances and sperm quality traits. Our analysis identified 283,382 piRNAs, 1,355 of which correlated to at least one semen quality trait. Indeed, genome analysis of the correlated piRNAs evidenced that 57% of these were less than 50kb apart and were significantly enriched near Long Interspersed Nuclear Elements (LINEs). Moreover, some of the significant piRNAs mapped within or close to genes relevant for fertility or spermatogenesis such asCSNK1G2andPSMF1.
Implementation of Lot Quality Assurance Sampling Using Mobile Data Collection Tools to Assess Vaccination Coverage After Synchronized Polio Vaccination in the Province of Camiguin, Philippines
Authors: Gonzales Ian Christian A. 
Published: March 2020

ABSTRACTObjectivesThe study assessed immunization coverage after one round of synchronized Polio vaccination in Camiguin, Philippines. It included classifying the coverage level, identifying the level of awareness and source of information for the campaign, describing the reasons for non-vaccination, and pilot a mobile data collection platform.MethodsLot Quality Assurance Sampling (LQAS) is a household survey using a multi-stage clustered technique. Sixty respondents per municipality, divided into 6 clusters, with one barangay considered as one cluster. Barangays were selected with probability proportional to size. Households were taken by systematic sampling. One child was randomly selected if there were multiple children in a household. Data collection was done using KoBo Toolbox.ResultsThe municipalities of Mahinog and Sagay had two unvaccinated children each. Guinsiliban and Mambajao only had one unvaccinated child each. Catarman did not have any unvaccinated child. The reasons for non-vaccination were the lack of means of validation, fear of side effects, and the absence of a caregiver at the time of vaccination. The most common sources of information were health workers and television.DiscussionCoverage for all five municipalities of the province passed the decision value. The main reason for non-vaccination was the lack of means of validation, which emphasizes the need for high quality finger marking and the provision of vaccination cards. Only Mahinog did not pass the threshold for campaign awareness. LQAS is useful for validating areas with concerns on the set target population and administrative coverage. Mobile data collection through KoBo ToolBox is a useful method for field use. It is easily adaptable, user-friendly, and allows for immediate data validation and analysis.
Change in outbreak epicenter and its impact on the importation risks of COVID-19 progression: a modelling study
Authors: Adegboye Oyelola A , Adekunle Adeshina I , Pak Anton , Gayawan Ezra , Leung Denis HY , Rojas Diana P , Elfaki Faiz , McBryde Emma S , Eisen Damon P 
Published: March 2020

AbstractThe outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) that originated in the city of Wuhan, China has now spread to every inhabitable continent, but now theattention has shifted from China to other epicenters, especially Italy. This study explored the influence of spatial proximities and travel patterns from Italy on the further spread of SARS-CoV-2 around the globe. We showed that as the epicenter changes, the dynamics of SARS-CoV-2 spread change to reflect spatial proximities.
How to improve adherence with quarantine: Rapid review of the evidence
Authors: Webster Rebecca K. , Brooks Samantha K. , Smith Louise E. , Woodland Lisa , Wessely Simon , Rubin G. James 
Published: March 2020

AbstractObjectivesThe January 2020 outbreak of coronavirus has once again thrown the vexed issue of quarantine into the spotlight, with many countries asking their citizens to ‘self-isolate’ if they have potentially come into contact with the infection. However, adhering to quarantine is difficult. Decisions on how to apply quarantine should be based on the best available evidence to increase the likelihood of people adhering to protocols. We conducted a rapid review to identify factors associated with adherence to quarantine during infectious disease outbreaks.Study designRapid evidence review.MethodsWe searched Medline, PsycINFO and Web of Science for published literature on the reasons for and factors associated with adherence to quarantine during an infectious disease outbreak.ResultsWe found 3163 papers and included 14 in the review. Adherence to quarantine ranged from as little as 0 up to 92.8%. The main factors which influenced or were associated with adherence decisions were the knowledge people had about the disease and quarantine procedure, social norms, perceived benefits of quarantine and perceived risk of the disease, as well as practical issues such as running out of supplies or the financial consequences of being out of work.ConclusionsPeople vary in their adherence to quarantine during infectious disease outbreaks. To improve this, public health officials should provide a timely, clear rationale for quarantine and information about protocols; emphasise social norms to encourage this altruistic behaviour; increase the perceived benefit that engaging in quarantine will have on public health; and ensure that sufficient supplies of food, medication and other essentials are provided.
Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial
Authors: Chen Chang , Zhang Yi , Huang Jianying , Yin Ping , Cheng Zhenshun , Wu Jianyuan , Chen Song , Zhang Yongxi , Chen Bo , Lu Mengxin , Luo Yongwen , Ju Lingao , Zhang Jingyi , Wang Xinghuan 
Published: March 2020

AbstractBackgroundNo clinically proven effective antiviral strategy exists for the epidemic Coronavirus Disease 2019 (COVID-19).MethodsWe conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Patients were randomly assigned in a 1:1 ratio to receive conventional therapy plus Umifenovir (Arbidol) (200mg*3/day) or Favipiravir (1600mg*2/first day followed by 600mg*2/day) for 10 days. The primary outcome was clinical recovery rate of Day 7. Latency to relief for pyrexia and cough, the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV) were the secondary outcomes. Safety data were collected for 17 days.Results240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive Favipiravir (116 assessed), and 120 to receive Arbidol (120 assessed). Clinical recovery rate of Day 7 does not significantly differ between Favipiravir group (71/116) and Arbidol group (62/120) (P=0.1396, difference of recovery rate: 0.0954; 95% CI: -0.0305 to 0.2213). Favipiravir led to shorter latencies to relief for both pyrexia (difference: 1.70 days, P<0.0001) and cough (difference: 1.75 days, P<0.0001). No difference was observed of AOT or NMV rate (both P>0.05). The most frequently observed Favipiravir-associated adverse event was raised serum uric acid (16/116, OR: 5.52, P=0.0014).ConclusionsAmong patients with COVID-19, Favipiravir, compared to Arbidol, did not significantly improve the clinically recovery rate at Day 7. Favipiravir significantly improved the latency to relief for pyrexia and cough. Adverse effects caused Favipiravir are mild and manageable. This trial is registered with Chictr.org.cn (ChiCTR2000030254).
The impact of unplanned school closure on children’s social contact: Rapid evidence review
Authors: Brooks Samantha K. , Smith Louise E. , Webster Rebecca K. , Weston Dale , Woodland Lisa , Hall Ian , Rubin G. James 
Published: March 2020

AbstractBackgroundEmergency school closures are often used as public health interventions during infectious disease outbreaks in an attempt to minimise the spread of infection. However, if children continue to mix with others outside the home during the closures, these measures are unlikely to be effective.ObjectivesThis review aimed to summarise existing literature on children’s activities and contacts made outside the home during unplanned school closures.MethodsWe searched four databases from inception to February 2020 for relevant literature. Main findings were extracted.Results3,343 citations were screened and 19 included in the review. Activities and social contacts appeared to decrease during closures but contact was still common. All studies reported children leaving the house or being looked after by non-household members. There was some evidence that older child age and parental disagreement with closure were predictive of children leaving the house, and mixed evidence regarding the relationship between infection status and leaving the home. Parental agreement with closure was generally high, but some parents disagreed due to perceived low risk of infection and practical issues regarding childcare and financial impact.ConclusionsEvidence suggests that many children continue to leave the house and mix with others during school closures despite public health recommendations to avoid social contact. This review of behaviour during unplanned school closures could be used to improve infectious disease modelling.
A Tool to Early Predict Severe Corona Virus Disease 2019 (COVID-19) : A Multicenter Study using the Risk Nomogram in Wuhan and Guangdong, China
Authors: Gong Jiao , Ou Jingyi , Qiu Xueping , Jie Yusheng , Chen Yaqiong , Yuan Lianxiong , Cao Jing , Tan Mingkai , Xu Wenxiong , Zheng Fang , Shi Yaling , Hu Bo 
Published: March 2020

AbstractBackgroundDue to no reliable risk stratification tool for severe corona virus disease 2019 (COVID-19) patients at admission, we aimed to construct an effective model for early identifying cases at high risk of progression to severe COVID-19.MethodsIn this retrospective three-centers study, 372 non-severe COVID-19 patients during hospitalization were followed for more than 15 days after admission. Patients who deteriorated to severe or critical COVID-19 and patients who kept non-severe state were assigned to the severe and non-severe group, respectively. Based on baseline data of the two groups, we constructed a risk prediction nomogram for severe COVID-19 and evaluate its performance.ResultsThe train cohort consisted of 189 patients, while the two independent validation cohorts consisted of 165 and 18 patients. Among all cases, 72 (19.35%) patients developed severe COVID-19. We found that old age, and higher serum lactate dehydrogenase, C-reactive protein, the coefficient of variation of red blood cell distribution width, blood urea nitrogen, direct bilirubin, lower albumin, are associated with severe COVID-19. We generated the nomogram for early identifying severe COVID-19 in the train cohort (AUC 0.912 [95% CI 0.846-0.978], sensitivity 85.71%, specificity 87.58%); in validation cohort (0.853 [0.790-0.916], 77.5%, 78.4%). The calibration curve for probability of severe COVID-19 showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analysis indicated that nomogram conferred high clinical net benefit.ConclusionOur nomogram could help clinicians to early identify patients who will exacerbate to severe COVID-19, which will enable better centralized management and early treatment of severe patients.SummaryOlder age; higher LDH, CRP, RDW, DBIL, BUN; lower ALB on admission correlated with higher odds of severe COVID-19. An effective prognostic nomogram composed of 7 features could allow early identification of patients at risk of exacerbation to severe COVID-19.
Modifiable lifestyle factors and risk of stroke: a Mendelian randomization analysis
Authors: Harshfield Eric L , Georgakis Marios K , Malik Rainer , Dichgans Martin , Markus Hugh S 
Published: March 2020

ABSTRACTAimsAssessing whether modifiable risk factors are causally associated with reduced stroke risk is important in planning public health measures, but determining causality can be difficult in epidemiological data. Leveraging large-scale genetic data in a technique known as Mendelian randomisation, we aimed to determine whether modifiable lifestyle factors including educational attainment, smoking, and body mass index are causal risk factors for ischaemic stroke and its different subtypes and haemorrhagic stroke.Methods and ResultsWe performed two-sample and multivariable Mendelian randomization to assess the causal effect of twelve lifestyle factors on risk of stroke and whether these effects are independent. We found genetic predisposition to increased number of years of education to be inversely associated with ischaemic, large-artery, and small-vessel stroke, as well as with intracerebral haemorrhage. Genetic predisposition to ever smoking regularly, higher body mass index (BMI), and higher waist-hip ratio are also associated with ischaemic and large-artery stroke. Additionally, we found that the effects of education, BMI, and smoking on ischaemic stroke to be independent of each other.ConclusionGenetic predisposition to higher educational attainment can reduce the risk of ischaemic, large-artery, and small-vessel stroke, while genetic predisposition to smoking and higher anthropometry measures can increase the risk of these stroke subtypes. This suggests that lifestyle modification addressing these risk factors will reduce stroke risk.
Sentinel Event Surveillance to Estimate Total Sars-CoV-2 Infections, United States
Authors: Lover Andrew A. , McAndrew Thomas 
Published: March 2020

AbstractHuman infections with a novel coronavirus (SARS-CoV-2) were first identified via syndromic surveillance in December of 2019 in Wuhan China. Since identification, infections (coronavirus disease-2019; COVID-19) caused by this novel pathogen have spread globally, with more than 180,000 confirmed cases as of March 16, 2020. Effective public health interventions, including social distancing, contact tracing, and isolation/quarantine rely on the rapid and accurate identification of confirmed cases. However, testing capacity (having sufficient tests and laboratory throughput) to support these non-pharmaceutical interventions remains a challenge for containment and mitigation of COVID-19 infections.We undertook a sentinel event strategy (where single health events signal emerging trends) to estimate the incidence of COVID-19 in the US. Data from a recent national conference, the Conservative Political Action Conference, (CPAC) near Washington, DC and from the outbreak in Wuhan, China were used to fit a simple exponential growth model to estimate the total number of incident SARS-CoV-2 infections in the United States on March 1, 2020, and to forecast subsequent infections potentially undetected by current testing strategies. Our analysis and forecasting estimates a total of 54,100 SARS-CoV-2 infections (80 % CI 5,600 to 125,300) have occurred in the United States to March 12, 2020.Our forecast predicts that a very substantial number of infections are undetected, and without extensive and far-reaching non-pharmaceutical interventions, the number of infections should be expected to grow at an exponential rate.
Estimating Cases of COVID-19 from Daily Death Data in Italy
Authors: Raheem Ali 
Published: March 2020

COVID-19 is an emerging infectious disease which has been declared a pandemic by the World Health Organisation. Due to limited testing capacity for this new virus, variable symptomatology the majority of infected showing non-specific mild or no symptoms it is likely current prevalence data is an underestimate.MethodsWe present an estimate of the number of cases of COVID-19 compared to the number of confirmed case in Italy based on the daily reported deaths and information about the incubation period, time from symptom onset to death and reported case fatality rate.ResultsOur model predicts that on the 31st of January 2020 when the first 3 infected cases had been identified by Italian authorise there were already nearly 30 cases in Italy, and by the 24th of February 2020 only 0.5% cases had been detected and confirmed by Italian authorities. While official statistics had 132 confirmed case we believe a more accurate estimate would be closer to 26000. With a case-doubling period of about 2.5 days.