bluuebunny/crossref_metadata_2025 huggingface dataset:
A journey upstream: Fluctuating platelet-specific genes in cell-free plasma as proof-of-concept for using ribonucleic acid sequencing to improve understanding of postinjury platelet biology
Authors: Kornblith Lucy Zumwinkle , Bainton Cedric M.V. , Fields Alexander T. , Matthay Zachary A. , Magid Nina T. , Nunez-Garcia Brenda , Prakash Arun , Kurien Philip A. , Callcut Rachael A. , Cohen Mitchell J. , Bainton Roland J.
Published: March 2020

BACKGROUND

The mechanisms of aberrant circulating platelet behavior following injury remain unclear. Platelets retain megakaryocyte immature ribonucleic acid (RNA) splicing and protein synthesis machinery to alter their functions based on physiologic signals. We sought to identify fluctuating platelet-specific RNA transcripts in cell-free plasma (CFP) from traumatic brain injury (TBI) patients as proof-of-concept for using RNA sequencing to improve our understanding of postinjury platelet behavior. We hypothesized that we could identify differential expression of activated platelet-specific spliced RNA transcripts from CFP of patients with isolated severe fatal TBI (fTBI) compared with minimally injured trauma controls (t-controls), filtered by healthy control (h-control) data sets.

METHODS

High-read depth RNA sequencing was applied to CFP from 10 patients with fTBI (Abbreviated Injury Scale [AIS] for head ≥3, AIS for all other categories <3, and expired) and five t-controls (Injury Severity Score ≤1, and survived). A publicly available CFP RNA sequencing data set from 23 h-controls was used to determine the relative steady state of splice-form RNA transcripts discoverable in CFP. Activated platelet-specific spliced RNA transcripts were derived from studies of ex vivo platelet activation and identified by splice junction presence greater than 1.5-fold or less than 0.67-fold ex vivo nonactivated platelet-specific RNA transcripts.

RESULTS

Forty-two differentially spliced activated platelet-specific RNA transcripts in 34 genes were altered in CFP from fTBI patients (both upregulated and downregulated).

CONCLUSION

We have discovered differentially expressed activated platelet-specific spliced RNA transcripts present in CFP from isolated severe fTBI patients that are upregulated or downregulated compared with minimally injured trauma controls. This proof-of-concept suggests that a pool of immature platelet RNAs undergo splicing events after injury for presumed modulation of platelet protein products involved in platelet function. This validates our exploration of injury-induced platelet RNA transcript modulation as an upstream “liquid biopsy” to identify novel postinjury platelet biology and treatment targets for aberrant platelet behavior.

LEVEL OF EVIDENCE

Diagnostic tests, level V.
The impact of state laws on motor vehicle fatality rates, 1999–2015
Authors: Notrica David M. , Sayrs Lois W. , Krishna Nidhi , Rowe Dorothy , Jaroszewski Dawn E. , McMahon Lisa E.
Published: March 2020

BACKGROUND

Motor vehicle crash (MVC) fatalities have been declining while states passed various legislation targeting driver behaviors. This study assesses the impact of state laws on MVC fatality rates to determine which laws were effective.

METHODS

Publically available data were collected on driver-related motor vehicle laws, law strengths, enactment years, and numbers of verified-trauma centers. Prospective data on crash characteristics and MVC fatalities 16 years or older from Fatality Analysis Reporting System 1999 to 2015 (n = 850) were obtained. Generalize Linear Autoregressive Modeling was used to assess the relative contribution of state laws to the crude MVC fatality rate while controlling for other factors.

RESULTS

Lowering the minimum blood alcohol content (BAC) was associated with largest declines for all ages, especially the older cohorts: 16 years to 20 years (B = 0.23; p < 0.001), 21 years to 55 years (B = 1.7; p < 0.001); 56 years to 65 years (B = 3.2; p < 0.001); older than 65 years (B = 4.1; p < 0.001). Other driving under the influence laws were also significant. Per se BAC laws accompanying a reduced BAC further contributed to declines in crude fatality rates: 21 years to 55 years (B = −0.13; p < 0.001); older than 65 years (B = −0.17; p < 0.05). Driving under the influence laws enhancing the penalties, making revocation automatic, or targeting social hosts had mixed effects by age. Increased enforcement, mandatory education, vehicle impoundment, interlock devices, and underage alcohol laws showed no association with declining mortality rates. Red light camera and seatbelt laws were associated with declines in mortality rates for all ages except for older than 65 years cohort, but speed camera laws had no effect. Graduated Driver License laws were associated with declines for 16 years to 21 years (B = −0.06; p < 0.001) only. Laws targeting specific risks (elderly, motorcycles, marijuana) showed no effect on declining MVC mortality rates during the study period.

CONCLUSION

States have passed a wide variety of laws with varying effectiveness. A few key laws, specifically laws lowering allowable BAC, implementing red light cameras, and mandating seatbelt use significantly reduced MVC mortality rates from 1999 to 2015. Simply adding more laws/penalties may not equate directly to lives saved. Continued research on state laws will better inform policy makers to meet evolving public health needs in the management of MVC fatalities.

LEVEL OF EVIDENCE

Epidemiological, Level III.
Nocturia in Women With Type 2 Diabetes Mellitus
Authors: Wang Tzu-Ting , Chung Min-Huey , Chien Hung-Yu , Palmer Mary H. , Liao Chun-Ho , Liao Yuan-Mei
Published: March 2020

PURPOSE:

The first aim of this study was to compare nighttime voiding frequency (nocturia), serum hemoglobin A1clevel, peripheral neuropathy score, and global sleep quality score in younger (>40 to <65 years) versus older (≥65 years) women with type 2 diabetes mellitus (DM). Additional aims were to identify factors associated with clinically relevant nocturia (≥2 episodes/night) and to analyze relationships between nocturia frequency, glycemic control, peripheral neuropathy, and sleep quality in these women.

DESIGN:

Cross-sectional study.

SETTING AND SUBJECTS:

Participants were 118 women older than 40 years and with type 2 DM. Their mean age was 65.25 (SD = 9.66) years; the mean duration since diagnosis of type 2 DM was 10.96 (SD = 7.66) years. The study setting was 2 metabolism and endocrinology outpatient departments located in Taipei City and Taoyuan, Taiwan.

METHODS:

Data were collected using a questionnaire that queried sociodemographic information, lower urinary tract symptoms, and sleep quality. We also assessed peripheral neuropathy and lower extremity edema and obtained pertinent information from participants' medical records. Independentttests, multivariate logistic regression analyses, Spearman's rank correlation coefficients, and one-way analysis of variance were used to address the 3 study aims.

RESULTS:

Analyses found that older women (aged ≥65 years) had a significantly higher nighttime voiding frequency, a higher peripheral neuropathy score, and a higher sleep quality score than younger (>40 to <65 years) women. Multivariate logistic regression analyses identified 4 factors associated with clinically relevant nocturia advanced age, elevated hemoglobin A1clevel, suspected peripheral neuropathy, and lower extremity edema. Significant correlation coefficients were found between nighttime voiding frequency and serum hemoglobin A1clevels, peripheral neuropathy scores, and sleep quality scores. Analyses also found that women with a greater nocturia frequency had higher hemoglobin A1clevels, peripheral neuropathy scores, and sleep quality scores.

CONCLUSIONS:

Healthcare professionals should screen for nocturia in women with type 2 DM and provide appropriate management for those experiencing nocturia.
Ruegeria sediminis sp. nov., isolated from tidal flat sediment
Authors: Baek Jihye , Kim Jong-Hwa , Sukhoom Ampaitip , Kim Wonyong
Published: March 2020

A Gram-stain-negative, aerobic, non-motile, rod-shaped bacterial strain, designated CAU 1488T, was isolated from tidal flat sediment, and its taxonomic position was investigated using a polyphasic approach. The organism grew optimally at a temperature of 30 °C, at pH 7.0–7.5 and in the presence of 0–6 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CAU 1488T forms a lineage distinct from

Ruegeria marisrubri

ZGT 118T (97.9 %),

Ruegeria marina

ZH17T (97.6 %),

Ruegeria lacuscaerulensis

ITI 1157T (97.5 %),

Ruegeria pomeroyi

DSS-3T (97.1 %),

Ruegeria profundi

ZGT108T (97.0 %),

Ruegeria intermedia

CC-GIMAT-2T (96.8 %),

Ruegeria atlantica

CECT 4292T (96.7 %) and

Ruegeria kandeliae

J95T (95.9 %). Genome sequencing revealed that CAU 1488T had a genome size of 4.23 Mbp and a G+C content of 63.2 mol%. Overall genome related indexes including average nucleotide identity and digital DNA–DNA hybridization values were 75.0–83.0 % and 26.2 %, which are below the cutoffs of 95 and 70 %, respectively, indicating that strain CAU 1488T represents a distinct species from the members of the genus

Ruegeria

. The predominant quinone was ubiquinone-10 (Q-10). The major fatty acids were summed feature 8 (C18 : 1
 ω7c/ω6c; 60.7 %) and its polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and unidentified aminolipids. On the basis of phenotypic, chemotaxonomic and genomic data, strain CAU 1488T constitutes a novel species of the genus

Ruegeria

, for which the name Ruegeria sediminis sp. nov. is proposed. The type strain is CAU 1488T (=KCTC 62996T=NBRC 113693T).
Maximum entropy method for estimating the reproduction number: An investigation for COVID-19 in China
Authors: Tao Yong
Published: March 2020

The key parameter that characterizes the transmissibility of a disease is the reproduction number R. If it exceeds 1, the number of incident cases will inevitably grow over time, and a large epidemic is possible. To prevent the expansion of an epidemic, R must be reduced to a level below 1. To estimate the reproduction number, the probability distribution function of the generation interval of an infectious disease is required to be available; however, this distribution is often unknown. In this letter, given the incomplete information for the generation interval, we propose a maximum entropy method to estimate the reproduction number. Based on this method, given the mean value and variance of the generation interval, we first determine its probability distribution function and in turn estimate the real-time values of reproduction number of COVID-19 in China. By applying these estimated reproduction numbers into the susceptible-infectious-removed epidemic model, we simulate the evolutionary track of the epidemic in China, which is well in accordance with that of the real incident cases. The simulation results predict that China’s epidemic will gradually tend to disappear by May 2020 if the quarantine measures can continue to be executed.
Development and validation of a rapid, single-step reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) system potentially to be used for reliable and high-throughput screening of COVID-19
Authors: Jiang Minghua , Pan Weihua , Aratehfar Amir , Fang Wenjie , Ling Liyan , Fang Hua , Daneshnia Farnaz , Yu Jian , Liao Wanqing , Pei Hao , Li Xiaojing , Lass-Flörl Cornelia
Published: March 2020

Objectives

Development and validation of a single-step and accurate reverse transcriptase loop-mediated isothermal amplification technique (RT-LAMP) for rapid identification of SARS COV-2 relative to commercial quantitative reverse transcriptase real-time PCR (qRT-PCR) assays to allow prompt initiation of proper medical care and containment of virus spread.

Methods

Primers showing optimal in-silico features were subjected to analytical sensitivity and specificity to assess the limit of detection (LOD) and cross-reaction with closely- and distantly-related viral species, and clinically prominent bacterial and fungal species. In order to evaluate the clinical utility, our RT-LAMP was subjected to a large number of clinical samples, including 213 negative and 47 positive patients, relative to two commercial quantitative RT-PCR assays.

Results

The analytical specificity and sensitivity of our assay was 100% and 500 copies/ml when serial dilution performed in both water and sputum. Subjecting our RT-LAMP assay to clinical samples showed a high degree of specificity (99.5%), sensitivity (91.4%), positive predictive value (97.7%), and negative predictive value (98.1%) when used relative to qRT-PCR. Our RT-LAMP assay was two times faster than qRT-PCR and is storable at room temperature. A suspected case that later became positive tested positive using both our RT-LAMP and the two qRT-PCR assays, which shows the capability of our assay for screening purposes.

Conclusions

We present a rapid RT-LAMP assay that could extend the capacity of laboratories to process two times more clinical samples relative to qRT-PCR and potentially could be used for high-throughput screening purposes when demand is increasing at critical situations.
Long-term efficacy and safety of single fecal microbiota transplantation for recurrent active ulcerative colitis
Authors: Fang Haiming , Fu Lian , Li Xuejun , Wang Jiajia , Xiong Kangwei , Su Yuan , Zhang Lijiu
Published: March 2020

Aims

To assess the long-term safety and efficacy of single fecal microbiota transplantation (FMT) for recurrent ulcerative colitis (UC).

Methods

20 UC patients were randomly divided into single FMT (n=10) and standard of care (SOC) (n=10) group. Patients in FMT group were just treated with single fresh FMT. Patients in SOC group with mild to moderate UC were treated with mesalazine, those with severe UC were given corticosteroids-induced remission, mesalazine maintenance treatment. The primary endpoint was clinical and mucosal remission at week 8. The second endpoint was the maintenance of clinical and mucosal remission, and possible adverse events during the long term follow up (12 to 24 months).

Results

90% (9/10) patients in FMT group and50% (5 /10)in SOC group could achieve primary endpoint at week-8.After 12 months of follow-up, 66.7% (6/9) FMT initial responder and 80.0% (4/5) SOC initial responder could maintain remission.5 FMT initial responder recipients and5SOC initial responder completed 24-months follow up and mainly could maintain remission [FMT vs SOC580% (4/5) vs 60% (3/5)].No adverse events occurred post FMT during long-term follow-up. At Phylum level,Bacteroidetes, FirmicutesandProteobacteriawere the dominant bacteria of gut microbiota in active UC patients. Compared with donor, the relative abundance ofBacteroidetesdecreased andProteobacteriaincreased significantly in active UC patients,Firmicutesshowed no significant changes. Single fresh FMT could effectively reconstruct the composition of gut microbiota in active UC and maintain stability level with increasedBacteroidetesand decreasedProteobacteriaabundance. FMT significantly reduced the relative abundance ofEscherichiaand increased the relative abundance ofPrevotellaat genera level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, pantothenate and CoA biosynthesis showed significantly differences.

Conclusions

Single fresh FMT is an effective and safe strategy to induce long-term remission in patients with active UC and could be expected to be an alternative induction therapy for recurrent UC, even primary UC.

What does this paper add to the literature?

FMT is an effective and safe therapy for UC. However, long-term efficacy and safety of a single FMT was very limited. The present study found that a single fresh FMT could induce long-term remission in UC with no drugs need and could be expected to be an alternative induction therapy for recurrent UC, even primary UC
Advance of Novel Coronavirus Registration Clinical Trial
Authors: Song Gao , Cheng Meng Qun , Wei Xian Wen
Published: March 2020

Background

To 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 treatment

Methods

Statistics 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.

Results

232 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.

Conclusions

Different 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

Genome-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

1

Europe 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

The 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

Piwi-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

Objectives

The 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.

Methods

Lot 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.

Results

The 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.

Discussion

Coverage 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

The 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

Objectives

The 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 design

Rapid evidence review.

Methods

We 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.

Results

We 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.

Conclusions

People 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

Background

No clinically proven effective antiviral strategy exists for the epidemic Coronavirus Disease 2019 (COVID-19).

Methods

We 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.

Results

240 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).

Conclusions

Among 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

Background

Emergency 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.

Objectives

This review aimed to summarise existing literature on children’s activities and contacts made outside the home during unplanned school closures.

Methods

We searched four databases from inception to February 2020 for relevant literature. Main findings were extracted.

Results

3,343 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.

Conclusions

Evidence 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

Background

Due 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.

Methods

In 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.

Results

The 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.

Conclusion

Our 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.

Older 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

Aims

Assessing 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 Results

We 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.

Conclusion

Genetic 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

Abstract

Human 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.

Methods

We 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.

Results

Our 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.
Microbial Production Of Ellagic Acid From Mango Pulp Processing Waste
Authors: Rubavathi Anandan , Murugan Athiappan , Visali Kannan
Published: March 2020

Ellagic acid has gained momentum recently due to its various properties like anti-mutagenic, anti-carcinogenic, anti-oxidant, and anti-viral and many other benefits to human health. The present study focused on the microbial production of ellagic acid from mango pulp processing industrial waste an alternate method for conventional chemical extraction. Our experiments demonstrated that the 100 μg/ml of ellagic acid was produced byMicrococcus luteusfrom 9% of mango pulp waste and the optimization of ellagic acid production with Pontecorvo medium supplemented with 5.0 g of ellagitannin has yielded 37.80 ± 0.30 mg/g at pH 5.0, temperature 30 °C, ammonium nitrate (nitrogen source), glucose (carbon source), with 1.5% of inoculums after 24 h of incubation. Ellagic acid synthesized was further confirmed with the standard ellagic acid. Applications like drought resistant in plants, anti-microbial activity, anti-parasitic activity and anti-cancer activities have been proven. Ellagic acid exhibited potential applications and further research in product development is promising.
Genetics of recombination rate variation in the pig
Authors: Johnsson Martin , Whalen Andrew , Ros-Freixedes Roger , Gorjanc Gregor , Chen Ching-Yi , Herring William O. , de Koning Dirk-Jan , Hickey John M.
Published: March 2020

Background

In this paper, we estimated recombination rate variation within the genome and between individuals in the pig using multiocus iterative peeling for 150,000 pigs across nine genotyped pedigrees. We used this to estimate the heritability of recombination and perform a genome-wide association study of recombination in the pig.

Results

Our results confirmed known features of the pig recombination landscape, including differences in chromosome length, and marked sex differences. The recombination landscape was repeatable between lines, but at the same time, the lines also showed differences in average genome-wide recombination rate. The heritability of genome-wide recombination was low but non-zero (on average 0.07 for females and 0.05 for males). We found three genomic regions associated with recombination rate, one of them harbouring theRNF212gene, previously associated with recombination rate in several other species.

Conclusion

Our results from the pig agree with the picture of recombination rate variation in vertebrates, with low but nonzero heritability, and a major locus that is homologous to one detected in several other species. This work also highlights the utility of using large-scale livestock data to understand biological processes.
The protector within: Comparative genomics of APSE phages across aphids reveals rampant recombination and diverse toxin arsenals
Authors: Rouïl Jeff , Jousselin Emmanuelle , d’acier Armelle Coeur , Cruaud Corinne , Manzano-Marín Alejandro
Published: March 2020

Phages can fundamentally alter the physiology and metabolism of their hosts. While ubiquitous in the bacterial world, they have seldom been described among endosymbiotic bacteria. One notable exception in the APSE phage that is found associated with the gammaproteobacterialHamiltonella defensa, hosted by several insect species. This secondary facultative endosymbiont is not necessary for the survival of its hosts but can infect certain individuals or even whole populations. Its infection in aphids is often associated with protection against parasitoid wasps. This protective phenotype has actually been linked to the infection of the symbiont strain with an APSE, which carries a toxin cassette that varies among so-called ”types”. In the present work, we seek to expand our understanding of the diversity of APSE phages as well as the relations of theirHamiltonellahosts. For this, we assembled and annotated the full genomes of 16 APSE phages infectingHamiltonellasymbionts across 10 insect species. Molecular and phylogenetic analyses suggest that recombination has occurred repeatedly among lineages. Comparative genomics of the phage genomes revealed two variable regions that are useful for phage typing. Additionally, we find that mobile elements could play a role in the acquisition of new genes in the toxin cassette. Altogether, we provide an unprecedented view of APSE diversity and their genome evolution across aphids. This genomic investigation will provide a valuable resource for the design and interpretation of experiments aiming at understanding the protective phenotype these phages confer to their insect hosts.
Bioconversion of Mango Pulp Industrial Waste into Ellagic acid UsingAspergillus niger
Authors: Murugan Athiappan , Rubavathi Anandan , Kannan Visali , Parthiban Aurumugam
Published: March 2020

Ellagic acid was considered as the potential bioactive compound with many therapeutical applications. Bioconversion of tannin present in the mango pulp processing waste in to ellagic acid using fungi would be better alternate than the chemical as well as extraction from plant sources. A total of three different fungi were isolated from the soil sample and it was confirmed asAspergillus niger. Further, the isolated strains ofA. nigerwere identified to produce ellagic acid from ellagitannin of mango waste. Quantification of the ellagic acid production was carried out by solid-state fermentation using 3% of mango waste as substrate. Ellagic acid enzyme activity was calculated and found to be 17.6 U ml−1The ellagic acid production was optimized to fix the various factors, that is, pH and temperature, nitrogen and carbon source. The maximum production (200 μg/g) of ellagic acid was achieved at pH 5.5, temperature 30 °C, Ammonium nitrate as nitrogen source, 0.2% of NaCl and carbon source (0.2% of sugar) with 3% of mango pulp waste. Ellagic acid produced was characterized by UV–vis spectrophotometer and by FT-IR analysis.
High transmissibility of COVID-19 near symptom onset
Authors: Cheng Hao-Yuan , Jian Shu-Wan , Liu Ding-Ping , Ng Ta-Chou , Huang Wan-Ting ,   for Taiwan COVID-19 outbreak investigation team, Lin Hsien-Ho
Published: March 2020

Background

The dynamics of coronavirus disease 2019 (COVID-19) transmissibility after symptom onset remains unknown.

Methods

We conducted a prospective case-ascertained study on laboratory-confirmed COVID-19 cases and their contacts. Secondary clinical attack rate (considering symptomatic cases only) was analyzed for different exposure windows after symptom onset of index cases and for different exposure settings.

Results

Thirty-two confirmed patients were enrolled and 12 paired data (index-secondary cases) were identified among the 1,043 contacts. The secondary clinical attack rate was 0.9% (95% CI 0.5–1.7%). The attack rate was higher among those whose exposure to index cases started within five days of symptom onset (2.4%, 95% CI 1.1–4.5%) than those who were exposed later (zero case from 605 close contacts, 95% CI 0–0.61%). The attack rate was also higher among household contacts (13.6%, 95% CI 4.7–29.5%) and non- household family contacts (8.5%, 95% CI 2.4–20.3%) than that in healthcare or other settings. The higher secondary clinical attack rate for contacts near symptom onset remained when the analysis was restricted to household and family contacts. There was a trend of increasing attack rate with the age of contacts (p for trend < 0.001).

Conclusions

High transmissibility of COVID-19 near symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized social distancing measures are required. Rapid reduction of transmissibility over time implies that prolonged hospitalization of mild cases might not be necessary in large epidemics.