bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta-analysis of the clinical performance of commercial SARS-CoV-2 nucleic acid, antigen and antibody tests up to 22 August 2020
Authors: Van Walle I , Leitmeyer K , Broberg E K 
Published: September 2020

AbstractWe reviewed the clinical performance of SARS-CoV-2 nucleic acid, viral antigen and antibody tests based on 94739 test results from 157 published studies and 20205 new test results from 12 EU/EEA Member States. Pooling the results and considering only results with 95% confidence interval width ≤5%, we found 4 nucleic acid tests, among which 1 point of care test, and 3 antibody tests with a clinical sensitivity ≥95% for at least one target population (hospitalised, mild or asymptomatic, or unknown). Analogously, 9 nucleic acid tests and 25 antibody tests, among which 12 point of care tests, had a clinical specificity of ≥98%. Three antibody tests achieved both thresholds. Evidence for nucleic acid and antigen point of care tests remains scarce at present, and sensitivity varied substantially. Study heterogeneity was low for 8/14 (57.1%) sensitivity and 68/84 (81.0%) specificity results with confidence interval width ≤5%, and lower for nucleic acid tests than antibody tests. Manufacturer reported clinical performance was significantly higher than independently assessed in 11/32 (34.4%) and 4/34 (11.8%) cases for sensitivity and specificity respectively, indicating a need for improvement in this area. Continuous monitoring of clinical performance within more clearly defined target populations is needed.
Physiological Effect of Prone Positioning in Mechanically Ventilated SARS- CoV-2 Infected Patients with Severe ARDS: Preliminary Analysis of an Observational Study
Authors: Roy Avishek , Behera Srikant , Pande Aparna , Bhattacharjee Anirban , Bhattacharyya Amrita , Baidya Dalim K , Anand Rahul K , Ray Bikash R , Subramaniam Rajeshwari , Maitra Souvik 
Published: September 2020

AbstractProne position ventilation has been shown to decrease mortality and improve oxygenation in ARDS patients. With best of our knowledge, no study reported physiological effect of prone position in SARS-CoV-2 infected ARDS patients. In this prospective observational study, data of n=20 consecutive laboratory confirmed SARS-CoV-2 patients with severe ARDS as per Berlin definition was included. Data of 20 patients analyzed with a median (Interquartile range, IQR) age of 56 (45.5-67) y and median (IQR) P/F ratio of 56 (54-66) with a median (IQR) PEEP of 12 (12-14) before initiation of prone position. Seventy-five percentage (95% CI 53.1-88.8) patients were prone responders at 16h prone session and 50 (95% CI 29.9-70.1) % patients were sustained responders. There was a significant decrease in plateau airway pressure (p<0.0001), peak airway pressure (p<0.0001) and driving pressure(p<0.0001) and increase in static compliance (p=0.001), P/F ratio (p<0.0001), PaO2 (p=0.0002)and SpO2 (p=0.0004) at 4h and 16h since initiation of prone session and also after return of supine position. Prone position in SARS-CoV-2 infected severe ARDS patients is associated with improvement in lung compliance and oxygenation in two-third of the patients and persisted in half of the patients.
Influenza season 2019: analysis of 143 hospitalized cases
Authors: Bisso Indalecio Carboni , Prado Eduardo , Cantos Joaquin , Massó Agustín , Staneloni Inés , Román Eduardo San , Huespe Iván , Heras Marcos Las 
Published: September 2020

ABSTRACTIntroductionInfluenza virus infection is a latent public health problem, affecting millions of people through the planet, and it is an important cause of morbidity and mortality. In Argentina, there is a significant absence of data regarding influenza severe respiratory disease and, therefore, a lack of knowledge about the impact of this disease at health institutions.ObjectivesAnalysis of clinical characteristics, image findings and laboratory variables in patients with influenza viruses during 2019.MethodsRetrospective, single-centre study, we analyzed all confirmed cases of influenza in a high complexity hospital from Buenos Aires.Results143 patients with influenza virus were hospitalized in this period of time. The 98.6% were infected by type A influenza, and most of them 61.5% were H1N1 subtype.Median age was 71 years (IQR 60 - 82), 77.6% were older than 70 years, and 88.1% had at least one coexisting illness. 39.1% of the patients required intensive care, 11.1% invasive mechanical ventilation and 4.1% died during hospitalization.ConclusionMortality and severity were similar to previous series of non-pandemic influenza. Analysis of annual data would be valuable in order to document the severity of influenza hospitalizations by ageJgroup and comorbidities according to the circulating influenza viruses.
Variation of SARS-CoV-2 viral loads by sample type, disease severity and time: a systematic review
Authors: Edwards Thomas , Santos Victor S. , Wilson Anne L. , Cubas-Atienzar Ana I. , Kontogianni Konstantina , Williams Christopher T. , Adams Emily R. , Cuevas Luis E. 
Published: September 2020

ABSTRACTBackgroundTo describe whether SARS-CoV-2 viral loads (VLs) and cycle thresholds (CTs) vary by sample type, disease severity and symptoms duration.MethodsSystematic searches were conducted in MEDLINE, EMBASE, BioRxiv and MedRxiv. Studies reporting individual SARS-CoV-2 VLs and/or CT values from biological samples. Paired reviewers independently screened potentially eligible articles. CT values and VLs distributions were described by sample type, disease severity and time from symptom onset. Differences between groups were examined using Kruskal-Wallis and Dunn ‘s tests (post-hoc test). The risk of bias was assessed using the Joanna Briggs Critical Appraisal Tools.Results14 studies reported CT values, 8 VLs and 2 CTs and VLs, resulting in 432 VL and 873 CT data points. VLs were higher in saliva and sputum (medians 4.7×108 and 6.5×104 genomes per ml, respectively) than in nasopharyngeal and oropharyngeal swabs (medians 1.7×102 and 4.8×103). Combined naso/oropharyngeal swabs had lower CT values (i.e. higher VLs) than single site samples (p=<0.0001). CT values were also lower in asymptomatic individuals and patients with severe COVID-19 (median CT 30 for both) than among patients with moderate and mild symptoms (31.4 and 31.3, respectively). Stool samples were reported positive for a longer period than other specimens.ConclusionVLs are higher in saliva and sputum and in individuals who are asymptomatic of with severe COVID-19. Diagnostic testing strategies should consider that VLs vary by sample type, disease severity and time since symptoms onset.SummaryThis systematic review found a higher viral load in saliva and sputum than in nasopharyngeal swabs, in asymptomatic individuals and patients with severe COVID-19. Diagnostic testing strategies should consider the type of sample, disease severity and the time since symptoms onset.
Deep Learning Approach to Parse Eligibility Criteria in Dietary Supplements Clinical Trials Following OMOP Common Data Model
Authors: Bompelli Anusha , Li Jianfu , Xu Yiqi , Wang Nan , Wang Yanshan , Adam Terrence , He Zhe , Zhang Rui 
Published: September 2020

AbstractDietary supplements (DSs) have been widely used in the U.S. and evaluated in clinical trials as potential interventions for various diseases. However, many clinical trials face challenges in recruiting enough eligible patients in a timely fashion, causing delays or even early termination. Using electronic health records to find eligible patients who meet clinical trial eligibility criteria has been shown as a promising way to assess recruitment feasibility and accelerate the recruitment process. In this study, we analyzed the eligibility criteria of 100 randomly selected DS clinical trials and identified both computable and non-computable criteria. We mapped annotated entities to OMOP Common Data Model (CDM) with novel entities (e.g., DS). We also evaluated a deep learning model (Bi-LSTM-CRF) for extracting these entities on CLAMP platform, with an average F1 measure of 0.601. This study shows the feasibility of automatic parsing of the eligibility criteria following OMOP CDM for future cohort identification.
COVID-19 and human milk: SARS-CoV-2, antibodies, and neutralizing capacity
Authors: Pace Ryan M. , Williams Janet E. , Järvinen Kirsi M. , Belfort Mandy B. , Pace Christina D.W. , Lackey Kimberly A. , Gogel Alexandra C. , Nguyen-Contant Phuong , Kanagaiah Preshetha , Fitzgerald Theresa , Ferri Rita , Young Bridget , Rosen-Carole Casey , Diaz Nichole , Meehan Courtney L. , Caffe Beatrice , Sangster Mark Y. , Topham David , McGuire Mark A. , Seppo Antti , McGuire Michelle K. 
Published: September 2020

AbstractBackgroundIt is not known whether SARS-CoV-2 can be transmitted from mother to infant during breastfeeding, and if so whether the benefits of breastfeeding outweigh this risk. This study was designed to evaluate 1) if SARS-CoV-2 RNA can be detected in milk and on the breast of infected women, 2) concentrations of milk-borne anti-SARS-CoV-2 antibodies, and 3) the capacity of milk to neutralize SARS-CoV-2 infectivity.MethodsWe collected 37 milk samples and 70 breast swabs (before and after breast washing) from 18 women recently diagnosed with COVID-19. Samples were analyzed for SARS-CoV-2 RNA using RT-qPCR. Milk was also analyzed for IgA and IgG specific for the nucleocapsid protein, receptor binding domain (RBD), S2 subunit of the spike protein of SARS-CoV-2, as well as 2 seasonal coronaviruses using ELISA; and for its ability to neutralize SARS-CoV-2.ResultsWe did not detect SARS-CoV-2 RNA in any milk sample. In contrast, SARS-CoV-2 RNA was detected on several breast swabs, although only one was considered conclusive. All milk contained SARS-CoV-2-specific IgA and IgG, and levels of anti-RBD IgA correlated with SARS-CoV-2 neutralization. Strong correlations between levels of IgA and IgG to SARS-CoV-2 and seasonal coronaviruses were noted.ConclusionsOur data do not support maternal-to-child transmission of SARS-CoV-2 via milk; however, risk of transmission via breast skin should be further evaluated. Importantly, milk produced by infected mothers is a source of anti-SARS-CoV-2 IgA and IgG and neutralizes SARS-CoV-2 activity. These results support recommendations to continue breastfeeding during mild-to-moderate maternal COVID-19 illness.
SARS-CoV-2 antibody signatures robustly predict diverse antiviral functions relevant for convalescent plasma therapy
Authors: Natarajan Harini , Crowley Andrew R. , Butler Savannah E. , Xu Shiwei , Weiner Joshua A. , Bloch Evan M. , Littlefield Kirsten , Wieland-Alter Wendy , Connor Ruth I. , Wright Peter F. , Benner Sarah E. , Bonny Tania S. , Laeyendecker Oliver , Sullivan David , Shoham Shmuel , Quinn Thomas C. , Larman H. Benjamin , Casadevall Arturo , Pekosz Andrew , Redd Andrew D. , Tobian Aaron A.R. , Ackerman Margaret E. 
Published: September 2020

AbstractConvalescent plasma has emerged as a promising COVID-19 treatment. However, the humoral factors that contribute to efficacy are poorly understood. This study functionally and phenotypically profiled plasma from eligible convalescent donors. In addition to viral neutralization, convalescent plasma contained antibodies capable of mediating such Fc-dependent functions as complement activation, phagocytosis and antibody-dependent cellular cytotoxicity against SARS-CoV-2. These activities expand the antiviral functions associated with convalescent plasma and together with neutralization efficacy, could be accurately and robustly from antibody phenotypes. These results suggest that high-throughput profiling could be used to screen donors and plasma may provide benefits beyond neutralization.
Multifractal behavior of SARS-CoV2 COVID-19 pandemic spread, case of: Algeria, Russia, USA and Italy
Authors: Ouadfeul Sid-Ali 
Published: September 2020

SummaryHere, the multifractal behavior SARS-CoV2 COVID-19 pandemic daily and death cases is investigated through the so-called Wavelet Transform Modulus Maxima lines (WTMM) method, data of daily and death cases available via the World Health Organization (WHO) database of Algeria, Russia, USA and Italy is analyzed. The obtained results show the multifractal behavior of the COVID-19 pandemic spread data with different spectra of singularities.
Ranking the relative importance of COVID-19 immunisation strategies: a survey of expert stakeholders in Canada
Authors: Zhao Linlu , Ismail Shainoor J. , Tunis Matthew C. 
Published: September 2020

ABSTRACTBackgroundIn the face of anticipated limited COVID-19 vaccine supply necessitating the vaccination of certain groups earlier than others, the assessment of values and preferences of stakeholders is an important component of an ethically sound vaccine prioritisation framework.ObjectiveTo establish a preliminary expert stakeholder perspective on the relative importance of pandemic immunisation strategies for different COVID-19 pandemic scenarios at the time of initial COVID-19 vaccine availability.MethodsA survey was conducted by an email process from July 22 to August 14, 2020. Stakeholders included clinical and public health expert groups, provincial and territorial committees and national Indigenous groups, patient and community advocacy representatives and experts, health professional associations, and federal government departments in Canada. Survey results were analysed using descriptive statistics.ResultsOf 156 stakeholders contacted, 74 surveys were completed for a participation rate of 47.4%. During an anticipated period of initial vaccine scarcity for all pandemic scenarios, stakeholders generally considered the most important immunisation strategy to be protecting those who are most vulnerable to severe illness and death from COVID-19. This was followed in importance by the strategies to protect healthcare capacity, and to minimise transmission of COVID-19. In this supply constrained context, an immunisation strategy to protect critical infrastructure was considered the least important.ConclusionThe findings of this study provide a timely, preliminary Canadian expert perspective on priority COVID-19 pandemic immunisation strategies to guide early public health planning for an eventual COVID-19 immunisation program. These results fill a gap in the literature and could help advisory groups around the world in their assessment of values and preferences for ethical guidelines for COVID-19 vaccine allocation.
A self-assembled protein nanoparticle serving as a one-shot vaccine carrier
Authors: Wong Ten-Tsao , Liou Gunn-Guang , Kan Ming-Chung 
Published: September 2020

AbstractIn this paper, we are exploring the role of an amphipathic helical peptide in mediating the self-assembly of a fusion protein into a protein nanoparticle and the application of the nanoparticle as a one-shot vaccine carrier. Out of several candidates, an amphipathic helical peptide derived from M2 protein of type A influenza virus is found to stimulate high antigenicity when fused to a fluorescent protein genetically. This fusion protein was found to form protein nanoparticle spontaneously when expressed and purified protein stimulates long-lasting antibody responses in single immunization. Through modeling peptide structure and nanoparticle assembly, we have improved this vaccine carrier in complex stability. The revised vaccine carrier is able to stimulate constant antibody titer to a heterologous antigen for at least six months in single immunization. The immune response against a heterologous antigen can be boosted further by additional immunization in spite of high immune responses to carrier protein.
Sexually dimorphic influence of the circadian clock geneBmal1in the striatum on alcohol intake
Authors: de Zavalia Nuria , Schoettner Konrad , Goldsmith Jory A. , Solis Pavel , Ferraro Sarah , Parent Gabrielle , Amir Shimon 
Published: September 2020

SummaryThe geneBmal1(brain and muscle Arnt-like 1) plays an obligatory role in the generation of circadian rhythms in the suprachiasmatic nucleus (SCN), the master circadian clock in mammals [1–5]. Notably,Bmal1is widely expressed in mammalian brain [6], and perturbations inBmal1expression in select forebrain regions cause behavioral disturbances that are independent of the SCN, such as disturbances in sleep architecture, and in cognitive and affective behaviors [1, 7–15]. Interestingly, gene association studies in humans and in animals suggest thatBmal1may influence the propensity to consume alcohol, and that polymorphisms inBmal1may confer risk for alcohol dependence and related disorders [16–20]. However, research has not yet provided evidence of a causal role ofBmal1in the control of alcohol intake. We investigated voluntary alcohol consumption in conditional knockout mice that lackBmal1exclusively in the striatum, which is an important structure in the control of alcohol intake and preference [21–26]. Experiments were carried out in both male and female mice in order to account for the known sex differences in alcohol consumption [27–31] and in striatal functioning [32–36], as well as in the expression of clock genes and in the impact of circadian clocks on behavior [37–44]. We found that, in both males and females, selective deletion ofBmal1from principal medium spiny neurons (MSNs) of the striatum significantly altered voluntary alcohol intake and preference. Strikingly, the effect ofBmal1deletion was sexually dimorphic. Whereas in males, deletion ofBmal1augmented alcohol intake and preference, in females, the same deletion suppressed alcohol intake and preference. Interestingly, striatal deletion of the clock genePer2,which interacts withBmal1in the generation of circadian rhythms [4], and which has been shown to affect alcohol consumption in male mice [45], mimicked the effect ofBmal1deletion, albeit only in males. These results show thatBmal1in MSNs of the striatum exerts a sexually dimorphic influence on alcohol intake in mice, moderating intake in males, possibly viaPer2,and promoting heightened intake in females, independently ofPer2. We propose that a sexually dimorphic mechanism in the function ofBmal1in the striatum contributes to sex differences in the propensity to consume alcohol in mice. Whether such mechanism contributes to sex differences in other striatum-dependent appetitive and consummatory behaviors remains to be investigated.
Subcortical Atlas of the Rhesus Macaque (SARM) for Magnetic Resonance Imaging
Authors: Hartig Renée , Glen Daniel , Jung Benjamin , Logothetis Nikos K. , Paxinos George , Garza-Villarreal Eduardo A. , Messinger Adam , Evrard Henry C. 
Published: September 2020

AbstractDigitized neuroanatomical atlases are crucial for localizing brain structures and analyzing functional networks identified by magnetic resonance imaging (MRI). To aid in MRI data analysis, we have created a comprehensive parcellation of the rhesus macaque subcortex using a high-resolution ex vivo structural imaging scan. The structural scan and its parcellation were warped to the updated NIMH Macaque Template (NMT v2), an in vivo population template, where the parcellation was refined to produce the Subcortical Atlas of the Rhesus Macaque (SARM). The subcortical parcellation and nomenclature reflect those of the 4th edition of the Rhesus Monkey Brain in Stereotaxic Coordinates (RMBSC4; Paxinos et al., in preparation). The SARM features six parcellation levels, arranged hierarchically from fine regions-of-interest (ROIs) to broader composite regions, suited for fMRI studies. As a test, we ran a functional localizer for the dorsal lateral geniculate (DLG) nucleus in three macaques and found significant fMRI activation in this atlas region. The SARM has been made openly available to the neuroimaging community and can easily be used with common MR data processing software, such as AFNI, where the atlas can be embedded into the software alongside cortical macaque atlases.HighlightsWe present the Subcortical Atlas of the Rhesus Macaque (SARM).SARM provides a neuroanatomical reference frame for neuroimaging analysis.The entire subcortex is mapped, including the thalamus, basal ganglia, and brainstem.ROIs are grouped hierarchically, making SARM useful at multiple spatial resolutions.SARM is in the NMT v2 template space and complements the CHARM atlas for the cortex.
Genome-wide analysis of retinal transcriptome reveals common genetic network underlying perception of contrast and optical defocus detection
Authors: Tkatchenko Tatiana V. , Tkatchenko Andrei V. 
Published: September 2020

SUMMARYRefractive eye development is regulated by optical defocus in a process of emmetropization. Excessive exposure to negative optical defocus often leads to the development of myopia. However, it is still largely unknown how optical defocus is detected by the retina. Here, we used genome-wide RNA-sequencing (RNA-seq) to conduct analysis of the retinal genetic networks underlying contrast perception and refractive eye development. We report that the genetic network subserving contrast perception plays an important role in optical defocus detection and emmetropization. Our results demonstrate an interaction between contrast perception, the retinal circadian clock pathway and the signaling pathway underlying optical defocus detection. We also observe that the relative majority of genes causing human myopia are involved in the processing of optical defocus. Together, our results support the hypothesis that optical defocus is perceived by the retina using contrast as a proxy and provide new insights into molecular signaling underlying refractive eye development.
Data-driven multiplexed microtomography of endogenous subcellular dynamics
Authors: Jo YoungJu , Cho Hyungjoo , Park Wei Sun , Kim Geon , Ryu Donghun , Kim Young Seo , Lee Moosung , Joo Hosung , Jo HangHun , Lee Sumin , Min Hyun-seok , Heo Won Do , Park YongKeun 
Published: September 2020

AbstractSimultaneous imaging of various facets of intact biological systems across multiple spatiotemporal scales would be an invaluable tool in biomedicine. However, conventional imaging modalities have stark tradeoffs precluding the fulfilment of all functional requirements. Here we propose the refractive index (RI), an intrinsic quantity governing light-matter interaction, as a means for such measurement. We show that major endogenous subcellular structures, which are conventionally accessed via exogenous fluorescence labeling, are encoded in 3D RI tomograms. We decode this information in a data-driven manner, thereby achieving multiplexed microtomography. This approach inherits the advantages of both high-specificity fluorescence imaging and label-free RI imaging. The performance, reliability, and scalability of this technology have been extensively characterized, and its application within single-cell profiling at unprecedented scales has been demonstrated.