bluuebunny/crossref_metadata_2025 huggingface dataset:
What is the suitability of clinical vignettes in benchmarking the performance of online symptom checkers? An audit study
Authors: El-Osta Austen , Webber Iman , Alaa Aos , Bagkeris Emmanouil , Mian Saba , Sharabiani Mansour , Majeed Azeem
Published: August 2021

Objective

To assess the suitability of primary care vignettes in benchmarking the performance of online symptom checkers

Design

Observational study using publicly available, free online symptom checkers

Participants

Three symptom checkers (Healthily, Ada and Babylon) that provided consultations in English. 139 standardized patient vignettes were compiled by RCGP. Three independent GPs interpreted the vignettes to arrive at a “Gold Standard” consisting of 3 dispositions and divided into one of three categories of triage urgency: (1) emergency care required, (2) primary care required and (3) self-care.

Main outcome measures

Six professional non-medical and lay inputters simulated 2774 standardized patient evaluations using 3 online symptom checkers (OSC). We recorded when OSC provided a triage recommendation and whether it correctly recommended the appropriate triage recommendation across three categories of triage urgency (emergency care, primary care or self-care). We collected data on whether the solution appeared within the first 3 dispositions in each of the standards across 2774 standardized patient evaluations.

Results

When benchmarked against the Gold Standard, Healthily provided an appropriate triage recommendation 61.9% of the time compared to 45.3% and 42.4% of the time for Babylon and Ada respectively. There was poor agreement between OSC consultation outcome and Gold Standard dispositions. When compared to the Gold Standard, Healthily gave an unsafe “under-triage” recommendation 28.6% of the time overall across the three categories compared to 43.3% for Ada and 47.5% for Babylon (P<0.001).

Conclusions

OSCs recommended ‘very unsafe’ triages only <4% of the time suggesting that the online consultation tools are generally working at a safe level of risk. Primary care vignettes are a helpful tool to support development of OSC, but not ideally suited to benchmark the performance of different OSC. Real-world evidence studies involving general practice are recommended to benchmark the performance of OSC in the community setting.

Strengths and limitations of this study

139 independently created primary care vignettes covering 18 subcategories of primary care were used to benchmark the performance of three online symptom checkers using 2774 unique patient simulations

A gold standard for each primary care vignette was derived using GP roundtables and single blinded testing

We investigated the extent that different inputters using the same vignette and online symptom checker received differing consultation outcomes and triage recommendations

We developed an accuracy matrix to objectively monitor online symptom checker consultation outcome and the safety of the triage recommendation

Limitations included a different number of inputters to simulate patients across the three online symptom checkers tested
Comparison of reported main COVID-19 information sources in national and culturally and linguistically diverse communities in Australia
Authors: Ayre J , Muscat DMM , Mac O , Batcup C , Cvejic E , Pickles K , Dolan H , Bonner C , Mouwad D , Zachariah D , Turalic U , Santalucia Y , Chen T , Vasic G , McCaffery K
Published: August 2021

Background

To manage the COVID-19 pandemic effectively, governments need clear and effective communication. This is a challenge for culturally diverse communities as groups may have different informational needs and information-seeking behaviours. In this paper we present the frequency of information sources for COVID-19 in a culturally diverse area of Sydney, Australia.

Methods

This study reports findings from two surveys. The first recruited participants across 10 languages between March 21 and July 9, 2021. The second provides a point of reference, and was an Australian, nationally-representative sample of English-speaking participants between November 4 – 18, 2020.

Results

For the survey in culturally and linguistically diverse communities, of 708 participants, mean age was 45.4 years (SE 0.78), and 51% of respondents were female. Across all language groups, 54.7% of participants used Australian official or public broadcasters to find out about COVID-19 (n=421). Australian commercial information sources (54.1%, n=417), social media (51.6%, n=397), and family and friends in Australia (32.7%, n=252) were common sources. Patterns varied substantially across language groups. In the nationally representative survey (n=2313), 67% of participants (n=1540) used Australian official or public broadcasters, with lower proportions for social media (31.9%, n=738) and friends, family or other personal sources (23.1%; n=533).

Conclusion

Almost 50% of participants from culturally and linguistically diverse communities did not report using Australian official or public broadcaster as main sources of information. Instead Australian commercial information sources, friends and family, overseas sources and social media were common. Though a crude comparison of the two datasets, this data can guide policy decisions for communication to different community groups. Further analysis is needed to interpret this data. Better understanding of how diverse communities seek and receive COVID-19 health information is imperative as we manage the current COVID-19 outbreak in the Sydney region.
Muscle microRNAs in the cerebrospinal fluid predict clinical response to nusinersen therapy in type II and type III spinal muscular atrophy patients
Authors: Magen Iddo , Aharoni Sharon , Yacovzada Nancy Sarah , Latzer Itay Tokatly , Alves Christiano R R , Sagi Liora , Fattal-Valevski Aviva , Swoboda Kathryn J , Katz Jacob , Bruckheimer Elchanan , Nevo Yoram , Hornstein Eran
Published: August 2021

Objective

The antisense oligonucleotide nusinersen (spinraza) regulates splicing of thesurvival motor neuron 2(SMN2)messenger RNA to increase SMN protein expression and has improved ventilator free survival and motor function outcomes in infantile onset forms of SMA, treated early in the course of the disease. However, the response in later onset forms of SMA is highly variable and dependent on symptom severity and disease duration at treatment initiation. Therefore, we aimed to identify novel noninvasive biomarkers that could predict the response to nusinersen in type II and III SMA patients.

Methods

34 SMA patients were included. We applied next-generation sequencing to identify microRNAs in the cerebrospinal fluid (CSF) as candidate biomarkers predicting response to nusinersen. Hammersmith Functional Motor Scale Expanded (HFMSE), was conducted at baseline and 6 months post initiation of nusinersen therapy to assess motor function. Patients changing by ≥ 3 or ≤0 points in the HFMSE total score were considered as responders or non-responders, respectively.

Results

Lower baseline levels of two muscle microRNAs (miR-206 and miR-133), alone or in combination, predicted the pre-determined clinical response to nusinersen after 6 months therapy. Moreover, miR-206 levels were inversely correlated with the HFMSE score.

Conclusions

Lower miR-206 and miR-133 in the CSF predict more robust clinical response to nusinersen treatment in later onset SMA patients. These novel findings have high clinical relevance for identifying early treatment response to nusinsersen in later onset SMA patients and call to test the ability of miRNAs to predict more sustained long-term benefit.
Specialized interferon ligand action in COVID19
Authors: Galbraith Matthew D. , Kinning Kohl T. , Sullivan Kelly D. , Araya Paula , Smith Keith P. , Granrath Ross E. , Shaw Jessica R. , Baxter Ryan , Jordan Kimberly R. , Russell Seth , Dzieciatkowska Monika , Reisz Julie A. , Gamboni Fabia , Cendali Francesca , Ghosh Tusharkanti , Monte Andrew A. , Bennett Tellen D. , Hansen Kirk C. , Hsieh Elena W.Y. , D’Alessandro Angelo , Espinosa Joaquin M.
Published: August 2021

The impacts of IFN signaling on COVID19 pathology are multiple, with protective and harmful effects being documented. We report here a multi-omics investigation of IFN signaling in hospitalized COVID19 patients, defining the biosignatures associated with varying levels of 12 different IFN ligands. Previously we showed that seroconversion associates with decreased production of select IFN ligands (Galbraith et al, 2021). We show now that the antiviral transcriptional response in circulating immune cells is strongly associated with a specific subset of ligands, most prominently IFNA2 and IFNG. In contrast, proteomics signatures indicative of endothelial damage associate with levels of IFNB and IFNA6. Differential IFN ligand production is linked to distinct constellations of circulating immune cells. Lastly, IFN ligands associate differentially with activation of the kynurenine pathway, dysregulated fatty acid metabolism, and altered central carbon metabolism. Altogether, these results reveal specialized IFN ligand action in COVID19, with potential diagnostic and therapeutic implications.

IMPACT STATEMENT

Analysis of multi-omics signatures associated with 12 different IFN ligands reveals their specialized action in COVID19.
Unrestricted Online Sharing of High-frequency, High-resolution Data on SARS-CoV-2 in Wastewater to Inform the COVID-19 Public Health Response in Greater Tempe, Arizona
Authors: Bowes Devin A. , Driver Erin M. , Kraberger Simona , Fontenele Rafaela S. , Holland LaRinda A. , Wright Jillian , Johnston Bridger , Savic Sonja , Newell Melanie Engstrom , Adhikari Sangeet , Kumar Rahul , Goetz Hanah , Binsfeld Allison , Nessi Kaxandra , Watkins Payton , Mahant Akhil , Zevitz Jake , Deitrick Stephanie , Brown Philip , Dalton Richard , Garcia Chris , Inchausti Rosa , Holmes Wydale , Tian Xiao-Jun , Varsani Arvind , Lim Efrem S. , Scotch Matthew , Halden Rolf U.
Published: August 2021

The COVID-19 pandemic prompted a global integration of wastewater-based epidemiology (WBE) into public health surveillance. Among early pre-COVID practitioners was Greater Tempe (population ~200,000), Arizona, where high-frequency, high-resolution monitoring of opioids began in 2018, leading to unrestricted online data release. Leveraging an existing, neighborhood-level monitoring network, wastewater from eleven contiguous catchment areas was analyzed by RT-qPCR for the SARS-CoV-2 E gene from April 2020 to March 2021 (n=1,556). Wastewater data identified an infection hotspot in a predominantly Hispanic and Native American community, triggering targeted interventions. During the first SARS-CoV-2 wave (June 2020), spikes in virus levels preceded an increase in clinical cases by 8.5±2.1 days, providing an early-warning capability that later transitioned into a lagging indicator (−2.0±1.4 days) during the December/January 2020-21 wave of clinical cases. Globally representing the first demonstration of immediate, unrestricted WBE data sharing and featuring long-term, innovative, high-frequency, high-resolution sub-catchment monitoring, this successful case study encourages further applications of WBE to inform public health interventions.
NSTEMI Decide: Development of a Decision Aid for Older Adults with Non ST Elevation Myocardial Infarction
Authors: Summapund Jenny , Sibley Rachel A. , Iqbal Sohah , Kiefer Nicholas J. , Langford Aisha , Spatz Erica , Barnett Mallory , Rivers Joshua , Chaudhry Sarwat I. , Dickson Victoria V. , Sikand Nikhil V. , Matlock Daniel D. , Dodson John A.
Published: August 2021

Background

Many patients hospitalized with non-ST elevation myocardial infarction (NSTEMI) are older adults (age ≥75), in whom invasive coronary angiography confers potential benefits but also higher risks than the general population. Our goal was to therefore develop a patient decision aid (PtDA) to assist with shared decision making (SDM) between cardiologists and older adults with this condition.

Methods

We followed International Patient Decision Aid Standards to develop the NSTEMI Decide PtDA. The initial prototype was based on structured interviews from 20 patients and 20 clinicians. Risks and benefits of invasive coronary angiography were derived from the available literature in older adults, with an emphasis on findings from randomized trials. The PtDA was then revised through an iterative, user-centered design approach with rapid prototyping using input from both clinician and patients to meet the needs of both stakeholders.

Results

The PtDA went through 8 iterations. The final decision aid was 11 pages and included background information (6 pages), explanation of benefits and risks (4 pages), and a summary (1 page). Large font (≥26 point) was used to accommodate visual difficulties. Language was tailored to an 8th grade reading level. Based on the best available literature, we included benefits of invasive coronary angiography (recurrent myocardial infarction, repeat revascularization) and risks (stroke, bleeding, acute kidney injury). The final PtDA was converted to a mobile health application to increase usability on portable digital devices in the clinical setting.

Conclusions

We developed the first PtDA tailored to older adults hospitalized with NSTEMI. This PtDA will be prospectively tested to evaluate dimensions including feasibility of use, satisfaction with care, medical knowledge, and decisional conflict.
Cardiovascular Disease Risk Prediction Models in Haiti: Implications for Primary Prevention in Low-Middle Income Countries
Authors: Yan Lily D , Pierre Jean Lookens , Rouzier Vanessa , Théard Michel , Apollon Alexandra , St-Preux Stephano , Kingery Justin R , Jamerson Kenneth A , Deschamps Marie , Pape Jean W , Safford Monika M , McNairy Margaret L
Published: August 2021

Background

Cardiovascular diseases (CVD) are rapidly increasing in low-middle income countries (LMICs). Accurate risk assessment is essential to reduce premature CVD by targeting primary prevention and risk factor treatment among high-risk groups. Available CVD risk prediction models are built on predominantly Caucasian, high-income country populations, and have not been evaluated in LMIC populations.

Objective

To compare the predicted 10-year risk of CVD and identify high-risk groups for targeted prevention and treatment in Haiti.

Methods

We used cross-sectional data within the Haiti CVD Cohort Study, including 653 adults ≥ 40 years without known history of CVD and with complete data. Six CVD risk prediction models were compared: pooled cohort equations (PCE), adjusted PCE with updated cohorts, Framingham CVD Lipids, Framingham CVD Body Mass Index (BMI), WHO Lipids, and WHO BMI. Risk factors were measured during clinical exams. Primary outcome was continuous and categorical predicted 10-year CVD risk. Secondary outcome was statin eligibility.

Results

Seventy percent were female, 65.5% lived on a daily income of ≤1 USD, 57.0% had hypertension, 14.5% had hypercholesterolemia, 9.3% had diabetes mellitus, 5.5% were current smokers, and 2.0% had HIV. Predicted 10-year CVD risk ranged from 3.9% in adjusted PCE (IQR 1.7-8.4) to 9.8% in Framingham-BMI (IQR 5.0-17.8), and Spearman rank correlation coefficients ranged from 0.87 to 0.98. The percent of the cohort categorized as high risk using the uniform threshold of 10-year CVD risk ≥ 7.5% ranged from 28.8% in the adjusted PCE model to 62.0% in the Framingham-BMI model (χ2= 331, p value < 0.001). Statin eligibility also varied widely.

Conclusions

In the Haiti CVD Cohort, there was substantial variation in the proportion identified as high-risk and statin eligible using existing models, leading to very different treatment recommendations and public health implications depending on which prediction model is chosen. There is a need to design and validate CVD risk prediction tools for low-middle income countries that include locally relevant risk factors.

Trial registration

clinicaltrials.govNCT03892265
Fractality of tics as a quantitative assessment tool for Tourette syndrome
Authors: Beeler Payton , Jensen Nicholas O. , Kim Soyoung , Robichaux-Viehoever Amy , Schlaggar Bradley L. , Greene Deanna J. , Black Kevin J. , Chakrabarty Rajan
Published: August 2021

Tics manifest as brief, purposeless, and unintentional movements or noises that, for many individuals, can be suppressed temporarily with effort. Peterson and Leckman (1998) hypothesized that the chaotic temporal nature of tics could possess an inherent fractality, that is, have neighbor-to-neighbor correlation at all levels of time scale. However, demonstrating this phenomenon has eluded researchers for more than two decades, primarily because of the challenges associated with estimating the scale-invariant, power law exponent – called the fractal dimension Df– from fractional Brownian noise. Here, we confirm this hypothesis and establish the fractality of tics by examining two tic time series datasets collected 6-12 months apart in children with tics, using one-dimensional random walk models. We find that Dfincreases from ∼1.4 to 1.75 in order of decreasing tic severity, and is correlated with tic severity as measured by the YGTTS total tic score. We demonstrate Dfto be a sensitive parameter in examining the effect of several tic suppression conditions on the tic time series. We confirm the fractal nature of tics in Tourette syndrome (TS) and extend the finding to Provisional Tic Disorder. Our findings pave the way for utilizing the fractal nature of tics as a robust quantitative tool for estimating tic severity and treatment effectiveness, as well as a marker for differentiating typical from functional tics.
Human gene function publications that describe wrongly identified nucleotide sequence reagents are unacceptably frequent within the genetics literature
Authors: Park Yasunori , West Rachael A , Pathmendra Pranujan , Favier Bertrand , Stoeger Thomas , Capes-Davis Amanda , Cabanac Guillaume , Labbé Cyril , Byrne Jennifer A
Published: August 2021

Nucleotide sequence reagents underpin a range of molecular genetics techniques that have been applied across hundreds of thousands of research publications. We have previously reported wrongly identified nucleotide sequence reagents in human gene function publications and described a semi-automated screening tool Seek & Blastn to fact-check the targeting or non-targeting status of nucleotide sequence reagents. We applied Seek & Blastn to screen 11,799 publications across 5 literature corpora, which included all original publications inGenefrom 2007-2018 and all original open-access publications inOncology Reportsfrom 2014-2018. After manually checking the Seek & Blastn screening outputs for over 3,400 human research papers, we identified 712 papers across 78 journals that described at least one wrongly identified nucleotide sequence. Verifying the claimed identities of over 13,700 nucleotide sequences highlighted 1,535 wrongly identified sequences, most of which were claimed targeting reagents for the analysis of 365 human protein-coding genes and 120 non-coding RNAs, respectively. The 712 problematic papers have received over 17,000 citations, which include citations by human clinical trials. Given our estimate that approximately one quarter of problematic papers are likely to misinform or distract the future development of therapies against human disease, urgent measures are required to address the problem of unreliable gene function papers within the literature.

Author summary

This is the first study to have screened the gene function literature for nucleotide sequence errors at the scale that we describe. The unacceptably high rates of human gene function papers with incorrect nucleotide sequences that we have discovered represent a major challenge to the research fields that aim to translate genomics investments to patients, and that commonly rely upon reliable descriptions of gene function. Indeed, wrongly identified nucleotide sequence reagents represent a double concern, as both the incorrect reagents themselves and their associated results can mislead future research, both in terms of the research directions that are chosen and the experiments that are undertaken. We hope that our research will inspire researchers and journals to seek out other problematic human gene function papers, as we are unfortunately concerned that our results represent the tip of a much larger problem within the literature. We hope that our research will encourage more rigorous reporting and peer review of gene function results, and we propose a series of responses for the research and publishing communities.
Internet of Things Architecture for Cellular Biology
Authors: Parks David F. , Voitiuk Kateryna , Geng Jinghui , Elliott Matthew A. T. , Keefe Matthew G. , Jung Erik A. , Robbins Ash , Baudin Pierre V. , Ly Victoria T. , Hawthorne Nico , Yong Dylan , Sanso Sebastian E. , Rezaee Nick , Sevetson Jess , Seiler Spencer T. , Currie Rob , Pollen Alex A. , Hengen Keith B. , Nowakowski Tomasz J. , Mostajo-Radji Mohammed A. , Salama Sofie R. , Teodorescu Mircea , Haussler David
Published: August 2021

The Internet of Things (IoT) provides a simple framework to easily control online devices. IoT is now a commonplace tool used by technology companies, but it is rarely used in biology experiments. IoT can benefit research through alarm notifications, automation, and the real-time monitoring of experiments. We developed and implemented an IoT architecture to control biological devices used in experiments. We developed our own electrophysiology, microscopy, and microfluidic devices so that may be controlled through a unified IoT architecture. The system allows each device to be monitored and controlled through an online web tool. We present our IoT architecture so other labs may replicate it for their own experiments.
Design and quality control of large-scale two-sample Mendelian randomisation studies
Authors: Haycock Philip C. , Borges Maria Carolina , Burrows Kimberly , Lemaitre Rozenn N. , Harrison Sean , Burgess Stephen , Chang Xuling , Westra Jason , Khankari Nikhil K. , Tsilidis Kostas , Gaunt Tom , Hemani Gib , Zheng Jie , Truong Therese , OMara Tracy , Spurdle Amanda B. , Law Matthew H. , Slager Susan L. , Birmann Brenda M. , Hosnijeh Fatemeh Saberi , Mariosa Daniela ,   ACCC,   CCFR-CORECT-GECCO,   EPITHYR,   InterLymph,   ECAC,   ILCCO,   KIDRISK,   PRACTICAL,   PanScan,   PanC4, Amos Chris I. , Hung Rayjean J. , Zheng Wei , Gunter Marc J. , Smith George Davey , Relton Caroline , Martin Richard M
Published: August 2021

Background

Mendelian randomization studies are susceptible to meta-data errors (e.g. incorrect specification of the effect allele column) and other analytical issues that can introduce substantial bias into analyses. We developed a quality control pipeline for the Fatty Acids in Cancer Mendelian Randomization Collaboration (FAMRC) that can be used to identify and correct for such errors.

Methods

We invited cancer GWAS to share summary association statistics with the FAMRC and subjected the collated data to a comprehensive QC pipeline. We identified meta data errors through comparison of study-specific statistics to external reference datasets (the NHGRI-EBI GWAS catalog and 1000 genome super populations) and other analytical issues through comparison of reported to expected genetic effect sizes. Comparisons were based on three sets of genetic variants:

1) GWAS hits for fatty acids, 2) GWAS hits for cancer and 3) a 1000 genomes reference set.

Results

We collated summary data from six fatty acid and 49 cancer GWAS. Meta data errors and analytical issues with the potential to introduce substantial bias were identified in seven studies (13%). After resolving analytical issues and excluding unreliable data, we created a dataset of 219,842 genetic associations with 87 cancer types.

Conclusion

In this large MR collaboration, 13% of included studies were affected by a substantial meta data error or analytical issue. By increasing the integrity of collated summary data prior to their analysis, our protocol can be used to increase the reliability of post-GWAS analyses. Our pipeline is available to other researchers via the CheckSumStats package (https://github.com/MRCIEU/CheckSumStats).
Measuring vaccine efficacy against infection and disease in clinical trials: sources and magnitude of bias in COVID-19 vaccine efficacy estimates
Authors: Williams Lucy R. , Ferguson Neil M. , Donnelly Christl A. , Grassly Nicholas C.
Published: August 2021

Background

Phase III trials have estimated COVID-19 vaccine efficacy (VE) against symptomatic and asymptomatic infection. We explore the direction and magnitude of potential biases in these estimates and their implications for vaccine protection against infection and against disease in breakthrough infections.

Methods

We developed a mathematical model that accounts for natural and vaccine-induced immunity, changes in serostatus and imperfect sensitivity and specificity of tests for infection and antibodies. We estimated expected biases in VE against symptomatic, asymptomatic and any SARS-CoV-2 infections and against disease following infection for a range of vaccine characteristics and measurement approaches, and the likely overall biases for published trial results that included asymptomatic infections.

Results

VE against asymptomatic infection measured by PCR or serology is expected to be low or negative for vaccines that prevent disease but not infection. VE against any infection is overestimated when asymptomatic infections are less likely to be detected than symptomatic infections and the vaccine protects against symptom development. A competing bias towards underestimation arises for estimates based on tests with imperfect specificity, especially when testing is performed frequently. Our model indicates considerable uncertainty in Oxford-AstraZeneca ChAdOx1 and Janssen Ad26.COV2.S VE against any infection, with slightly higher than published, bias-adjusted values of 59.0% (95% uncertainty interval [UI] 38.4 to 77.1) and 70.9% (95% UI 49.8 to 80.7) respectively.

Conclusion

Multiple biases are likely to influence COVID-19 VE estimates, potentially explaining the observed difference between ChAdOx1 and Ad26.COV2.S vaccines. These biases should be considered when interpreting both efficacy and effectiveness study results.
Preterm birth increases placental expression of multidrug resistance (MDR) transporters irrespective of prepregnancy body mass index (BMI)
Authors: Scott Hailey , Martinelli Lilian M , Bloise Enrrico , Connor Kristin L
Published: August 2021

Context

Preterm birth (PTB) and suboptimal prepregnancy body mass index (BMI) operate through inflammatory pathways to impair fetoplacental development. Placental efflux transporters mediate fetal protection and nutrition, however few studies consider the effect of both PTB and BMI on fetal protection. We hypothesized that PTB would alter the expression of placental multidrug resistance (MDR) transporters and selected pro-inflammatory cytokines, and that maternal underweight and obesity would further impair placental phenotype.

Objective

To determine whether placental MDR transporters P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP/ABCG2), and pro-inflammatory cytokine levels are altered by PTB and maternal BMI.

Design and Outcomes

A cross-sectional study was conducted to assess the effect of PTB (+/- chorioamnionitis), or the effect of maternal prepregnancy BMI on placental MDR transporter and interleukin [IL]-6 and 8 expression in 60 preterm and 36 term pregnancies.

Results

ABCB1 expression was increased in preterm compared to term placentae (p=0.04). P-gp (p=0.008) and BCRP (p=0.01) immunolabeling was increased among all preterm compared to term placentae, with P-gp expression further increased in preterm pregnancies with chorioamnionitis (PTC, p=0.007). Placental IL-6 mRNA expression was decreased in PTC compared to term placentae (p=0.0005), and PTC was associated with the greatest proportion of anti-inflammatory medications administered during pregnancy. Maternal BMI group did not influence placental outcomes.

Conclusions

PTB and infection, but not prepregnancy BMI, alter placental expression of MDR transporters and IL-6. This may have implications for fetal exposure to xenobiotics that may be present in the maternal circulation in pregnancies complicated by PTB.
COVID-19 in hospitalized patients in 4 hospitals in San Isidro, Buenos Aires, Argentina
Authors: Barra María Ana , Carlos Medinacelli Nelson Adolfo , Meza Padilla Camilo Andres , Di Rocco Lucrecia , Larrea Ramiro Manuel , Gaudenzi Giuliano , Mastrovincenzo Verónica Vanesa , Raña Elisa , Moreno Inés , Sörvik Dagmar Ana , Sarlingo Andrea , Dadomo Florencia , Torrilla Miguel
Published: August 2021

In December 2019, a novel illness called coronavirus disease 2019 (COVID-19) was described in China and became pandemic in a few months. The first case was detected in Argentina on March 3, 2020.

A multicentre prospective observational cohort study on hospitalized patients with COVID- 19 was conducted in 4 hospitals in San Isidro district from March 1, 2020 to October 31. Data was obtained by the attendant physician. 668 patients were included, the median age was 54 years, and 42.7% were female. Male sex and older age were associated with COVID-19 disease and more strongly with severity. Most frequent symptoms were fever and cough followed by dyspnoea, myalgia, odynophagia, headache, anosmia, and diarrhoea. Non-severe patients had more upper respiratory symptoms while severe patients had mainly lower respiratory symptoms on admission. Most common comorbidities were arterial hypertension, diabetes, and cardiovascular disease. A great proportion of patients had normal thorax X-ray and ground-glass opacity in tomography. In severe patients, radiography and tomography had a predominant ground – glass pattern, but normal radiography and tomography on presentation were present in 22% and 5.9%, respectively. The absence of fever and normal radiology on admission neither excluded the disease nor further severity. PCR elevation was related with COVID-19 disease and with severity, while lymphopenia was more related with the disease and leukocytosis and thrombocytopenia with severity. 8, 4% of patients were health care workers. The mortality rate was 12.4%, 32.7% in severe patients and 61.2% in ventilated patients. Mortality was higher in the public hospital, probably associated with patients with older age and more comorbidities. All these observations can contribute to the knowledge of this disease in terms of diagnosis and prognosis.
Binary toxin expression by Clostridioides difficile is associated with worse disease
Authors: Young Mary K. , Leslie Jhansi L. , Madden Gregory R. , Lyerly David M. , Carman Robert J. , Stewart David B. , Abhyankar Mayuresh M. , Petri William A.
Published: August 2021

Background

The incidence of Clostridioides difficile infection (CDI) has increased over the past two decades and is considered an urgent threat by the Centers for Disease Control. Hypervirulent strains such as ribotype 027, that possess genes for an additional toxin C. difficile binary toxin (CDT) are contributing to increased morbidity and mortality. In the mouse model, CDT activates Toll-like receptor 2 resulting in suppression of a protective type 2 innate immune response mediated by eosinophils.

Methods

We retrospectively tested stool from 215 CDI patients for CDT by enzyme-linked immunosorbent assay (ELISA). Stratifying patients by CDT status, we assessed if disease severity and clinical outcomes correlated with CDT positivity. Additionally, we performed 16 S rRNA gene sequencing to examine if CDT positive samples had an altered fecal microbiota.

Results

We found that patients with CdtB, the pore forming component of CDT, detected in their stool were more likely to have severe disease and had higher 90-day mortality compared to CDT negative patients. CDT positive patients also had higher C. difficile bacterial burden and white blood cell counts. There was no significant difference in gut microbiome diversity between CDT positive and negative patients.

Conclusions

Patients with fecal samples that were positive for CDT had increased disease severity and worse clinical outcomes. Utilization of PCR and C. difficile Toxins A and B testing may not reveal the entire picture when diagnosing CDI and the detection of CDT-expressing strains may be valuable during patient treatment.

We found that CDI patients with CDT detected in stool by immunoassay were more likely to have severe disease and had higher 90-day mortality.
TREATMENTS, RESOURCE UTILIZATION, AND OUTCOMES OF COVID-19 PATIENTS PRESENTING TO EMERGENCY DEPARTMENTS ACROSS PANDEMIC WAVES: AN OBSERVATIONAL STUDY BY THE CANADIAN COVID-19 EMERGENCY DEPARTMENT RAPID RESPONSE NETWORK (CCEDRRN)
Authors: Hohl Corinne M. , Rosychuk Rhonda J. , Hau Jeffrey P. , Hayward Jake , Landes Megan , Yan Justin W. , Ting Daniel K. , Welsford Michelle , Archambault Patrick M , Mercier Eric , Chandra Kavish , Davis Philip , Vaillancourt Samuel , Leeies Murdoch , Small Serena , Morrison Laurie J.
Published: August 2021

Background

Treatment strategies for coronavirus disease 2019 (COVID-19) evolved between pandemic waves. Our objective was to compare treatments, acute care resource utilization, and outcomes of COVID-19 patients presenting to Emergency Departments across two pandemic waves.

Methods

This observational study enrolled consecutive eligible COVID-19 patients presenting to 46 Emergency Departments participating in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) between March 1 and December 31, 2020. We collected data by retrospective chart review. Our primary outcome was in-hospital mortality. We used logistic regression modeling to assess the impact of pandemic wave on outcomes.

Results

We enrolled 9,967 patients in 8 provinces, 3,336 from the first and 6,631 from the second wave. Patients in the second wave were younger, fewer met criteria for severe COVID-19, and more were discharged from the Emergency Department. Adjusted for patient characteristics and disease severity, steroid use increased (odds ratio [OR] 8.0; 95% confidence interval [CI] 6.4 – 10.0), while the use of invasive mechanical ventilation decreased (OR 0.5; 95%CI 0.4 – 0.6) in the second wave. After adjusting for differences in patient characteristics and disease severity, the odds of hospitalization (OR 0.7; 95%CI 0.6 – 0.8) and critical care admission (OR 0.6; 95%CI 0.4 – 0.7) decreased, while mortality remained unchanged (OR 1.0; 95%CI 0.7-1.4).

Interpretation

In patients presenting to Canadian acute care facilities, rapid uptake of steroid therapy was evident. Mortality was stable despite lower critical care utilization in the second wave.

Trial Registration

Clinicaltrials.gov, NCT04702945
Three-dimensional printing of patient-specific lung phantoms for CT imaging: emulating lung tissue with accurate attenuation profiles and textures
Authors: Mei Kai , Geagan Michael , Roshkovan Leonid , Litt Harold I. , Gang Grace J. , Shapira Nadav , Stayman J. Webster , Noël Peter B.
Published: August 2021

Purpose

Phantoms are a basic tool for assessing and verifying performance in CT research and clinical practice. Patient-based realistic lung phantoms accurately representing textures and densities are essential in developing and evaluating novel CT hardware and software. This study introduces PixelPrint, a 3D printing solution to create patient-based lung phantoms with accurate attenuation profiles and textures.

Methods

PixelPrint, a software tool, was developed to convert Patient DICOM images directly into printer instructions (G-code). The density was modeled as the ratio of filament to voxel volume to emulate attenuation profiles for each voxel. A calibration phantom was designed to determine the mapping between filament line width and Hounsfield Units (HU) within the range of human lungs. For evaluation of PixelPrint, a phantom based on a human lung slice was manufactured and scanned with the same CT scanner and protocol used for the patient scan. Density and geometrical accuracy between phantom and patient CT data was evaluated for various anatomical features in the lung.

Results

For the calibration phantom, measured mean Hounsfield units show a very high level of linear correlation with respect to the utilized filament line widths, (r > 0.999). Qualitatively, the CT image of the patient-based phantom closely resembles the original CT image both in texture and contrast levels, with clearly visible vascular and parenchymal structures. Regions-of-interest (ROIs) comparing attenuation illustrated differences below 15 HU. Manual size measurements performed by an experienced thoracic radiologist reveal a high degree of geometrical correlation of details between identical patient and phantom features, with differences smaller than the intrinsic spatial resolution of the scans.

Conclusion

The present study demonstrates the feasibility of 3D printed patient-based lung phantoms with accurate organ geometry, image texture, and attenuation profiles. PixelPrint will enable applications in the research and development of CT technology, including further development in radiomics.
The association between statin and COVID-19 adverse outcomes: National COVID-19 cohort in South Korea
Authors: Chow Ronald , Lee Jihui , Noh Hyerim , Lee Jongseong , Shin Hyun Joon , Choi Young-Geun
Published: August 2021

Background

There currently exists limited and conflicting clinical data on the use of statins amongst COVID-19 patients. Given the both paucity and lack of consensus among data on statin’s efficacy and safety amongst COVID-19 patients, the current guideline is to continue statin in COVID-19 patients, who have previously been treated with statins. The aim of this paper was to compare hospitalized patients with COVID-19 who did and did not receive statins, in terms of COVID-19 outcomes.

Methods

We conducted population-based retrospective study using South Korea’s nationwide healthcare database as of May 15 2020. We identified 4,349 patients hospitalized with COVID-19 and aged 40 years or older. The cohort entry was defined as the date of hospitalization. Statin users were individuals with inpatient and outpatient prescription records of statins in the 240 days before cohort entry, and non-users were those without such records during this period. Our primary outcome was a composite endpoint of all-cause death, intensive care unit (ICU) admission, mechanical ventilation use and cardiovascular outcomes (myocardial infarction (MI), transient cerebral ischemic attacks (TIA) or stroke). We conducted inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis to estimate odds ratio (OR) and corresponding 95% confidence intervals (CI), to compare outcomes between statin users and non-users.

Findings

1,115 patients were statin users (mean age = 65.9 years; 60% female), and 3,234 were non-users (mean age = 58.3 years; 64% female). Statin use was not associated with increased risk of the primary outcome (IPTW OR 0.82; 95% CI: 0.60-1.11). Subgroup analysis showed a protective role of statins, for individuals with hypertension (IPTW OR 0.40; 95% CI: 0.23-0.69, p for interaction: 0.0087).

Interpretation

Given that statins are not detrimental and that it may be beneficial amongst hypertensive patients and relatively cheap, we would encourage further investigation into statin for the prevention and treatment of COVID-19.

Funding

YGC’s work was partially supported by 2020R1G1A1A01006229 awarded by the National Research Foundation of Korea.

Research in context

Evidence before this study

There is limited and conflicting data reporting on statin use among COVID-19 patients, and its association with COVID-19 outcomes

Added value of this study

We report no difference in COVID-19 outcomes between patients who used and did not use statins prior to COVID-19 diagnosis, except in hypertensive patients in which statins was shown to have a protective effect.

Implications of all the available evidence

As statins are not detrimental and relatively cheap, we encourage further investigation into statin for the prevention and treatment of COVID-19.
Safety and feasibility of research lumbar puncture in Huntington’s disease: the HDClarity cohort and bioresource
Authors: Rodrigues Filipe B , Owen Gail , Sathe Swati , Pak Elena , Kaur Dipinder , Ehrhardt Anka G , Lifer Sherry , Townhill Jenny , Schubert Katarzyna , Leavitt Blair R , Guttman Mark , Bang Jee , Lewerenz Jan , Levey Jamie ,   for the HDClarity Investigators, Sampaio Cristina , Wild Edward J
Published: August 2021

STRUCTURED ABSTRACT

Background

Biomarkers are needed to monitor disease progression, target engagement and efficacy in Huntington’s disease (HD). Cerebrospinal fluid (CSF) is an ideal medium to research such biomarkers due to its proximity to the brain.

Objectives

To investigate the safety and feasibility of research lumbar punctures (LP) in HD.

Methods

HDClarity (NCT02855476) is an ongoing international biofluid collection initiative built on the Enroll-HD platform, where clinical assessments are recorded. It aims to recruit 1,200 participants. Biosamples are collected following an overnight fast: blood via venipuncture and CSF via LP. Participants are healthy controls and HD gene expansion carriers across the disease spectrum. We report on monitored data from February 2016 to September 2019.

Results

Of 448 participants screened, 398 underwent at least 1 sampling visit, of which 98.24% were successful (i.e. CSF was collected), amounting to 10,610mL of CSF and 8,200mL of plasma. In the total 572 sampling visits, adverse events were reported in 24.13%, and headaches of any kind and post-LP headaches in 14.86% and 12.24%, respectively. Frequencies were less in manifest HD; gender, age, body mass index and disease burden score were not associated with the occurrence of the events in gene expansion carriers. Headaches and back pain were the most frequent adverse events.

Conclusions

HDClarity is the largest CSF collection initiative to support scientific research into HD and is now established as a leading resource for HD research. Our data confirm that research LP in HD are feasible and acceptable to the community, and have a manageable safety profile.
KNOWLEDGE AND RISK PERCEPTION OF NIGERIANS TOWARDS THE CORONAVIRUS DISEASE (COVID-19)
Authors: Udomah Bolaji Felicia , Ashaolu Uriel Oludare , Olomofe Charles Oluwatemitope , Dada Olufunke Folasade , Soyemi Victor Kehinde , Aremu-Kasumu Yetunde Bolatito , Ochieze Chikezie John , Adeyemi Ayodele Olusola , Owolabi Adeyinka Olabisi , Igbokwe Martin Chukwudum , Ajumuka Emmanuel Eziashi , Ologunde Kehinde Williams , Popoola Gbenga Omotade , Ariyo Olumuyiwa Elijah , Fayemi Olaniyi Bamidele
Published: August 2021

ABSTARCT

Background

The Coronavirus Disease 2019 (COVID-19) is far from over, although appreciable progress has been made to limit the devastating effects of the pandemic across the globe. Adequate knowledge and risk perception is a critical assessment that is required to ensure proper preventive measures. This study assessed these among Nigerians.

Methods

The study was a cross-sectional assessment of 776 consenting Nigerian adults that were distributed across the 6 geo-political zones and the Federal Capital Territory. Online pre-tested, semi-structured questionnaire were used to obtain the socio-demographic data and assessed the knowledge and risk perception of the participants to COVID-19. The knowledge of COVID-19 was assessed based on the number of accurate responses given in comparison to average scores. Chi-square analysis was computed to analysis the association between socio-demographic characteristics and knowledge of COVID-19 and risk perception. Data analysis was done using SPSS version 21, the level of significance was set at value p<0.05 at 95% confidence interval.

Results

Majority of the participants were male 451 (58.1%), there was a good knowledge of COVID-19 among 90.3% of respondents with 57% having positive risk perception. There was a statistically significant relationship between good knowledge and positive risk perception of COVID-19 (p < 0.001). Annual income (p =0.012) and the perception that “vaccines are good” significantly predict positive risk perception of COVID-19 among the respondents.

Conclusion

A good knowledge of COVID-19 and vaccination against the virus were the two most important factors that determined risk perception among the population. This may be because of the widespread advocacy, and it portends a good omen at combating COVID-19 menace.
Increased Autotaxin levels in severe COVID-19, correlating with IL-6 levels, endothelial dysfunction biomarkers, and impaired functions of dendritic cells
Authors: Nikitopoulou Ioanna , Fanidis Dionysios , Ntatsoulis Konstantinos , Moulos Panagiotis , Mpekoulis George , Evangelidou Maria , Vassiliou Alice G. , Dimakopoulou Vasiliki , Jahaj Edison , Tsipilis Stamatios , Orfanos Stylianos E. , Dimopoulou Ioanna , Angelakis Emmanouil , Akinosoglou Karolina , Vassilaki Niki , Tzouvelekis Argyris , Kotanidou Anastasia , Aidinis Vassilis
Published: August 2021

Autotaxin (ATX; ENPP2) is a secreted lysophospholipase D catalysing the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signalling phospholipid. Genetic and pharmacologic studies have previously established a pathologic role for ATX and LPA signalling in pulmonary injury, inflammation, and fibrosis. Here, increased ENPP2 mRNA levels were detected in immune cells from nasopharyngeal swab samples of COVID-19 patients, and increased ATX serum levels were found in severe COVID-19 patients. ATX serum levels correlated with the corresponding increased serum levels of IL-6 and endothelial damage biomarkers, suggesting an interplay of the ATX/LPA axis with hyperinflammation and the associated vascular dysfunction in COVID-19. Accordingly, dexamethasone (Dex) treatment of mechanically ventilated patients reduced ATX levels, as shown in two independent cohorts, indicating that the therapeutic benefits of Dex include the suppression of ATX. Moreover, large scale analysis of multiple single cell RNAseq datasets revealed the expression landscape of ENPP2 in COVID-19 and further suggested a role for ATX in the homeostasis of dendritic cells, that exhibit both numerical and functional deficits in COVID-19. Therefore, ATX has likely a multifunctional role in COVID-19 pathogenesis, worth of suggesting that its pharmacological targeting might represent an additional therapeutic option.