bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Aspirin and Other Nonsteroidal Anti-inflammatory Drugs With Vertebral Trabecular Bone: Data From Multiethnic Study of Atherosclerosis, a Population-Based Multicenter Cohort Study
Authors: Ahmad Khadije , Budoff Matthew J. , Delaney Joseph A. , Mao SongShou , Gao Yanlin , Nasir Khurram , Tracy Russell , Li Dong 
Published: July 2020

ObjectiveThe objective of this article was to study the association of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) with bone mineral density (BMD).MethodsSpine BMD was evaluated in a subset of 2028 participants from the Multiethnic Study of Atherosclerosis cohort who were NSAID users (including aspirin) and underwent both lumbar and thoracic imaging. Multiethnic Study of Atherosclerosis is a prospective cohort study that includes 4 ethnic groups (white, Asian, African American, and Hispanic). Trabecular BMD was evaluated by quantitative computed tomography based on cardiac computed tomography images, which were obtained during coronary calcium scans. The analyses were cross sectional using baseline examination data for exposure and outcomes.ResultsAfter adjustment for potential confounders including age, sex, race, and traditional cardiovascular risk factors, a small association between trabecular BMD and baseline use of COX-2–selective NSAID was observed. COX-2–selective NSAID use was associated with 7.4 mg/cm3(95% confidence interval [CI], 1.6–13.3;P= 0. 013) higher trabecular BMD in thoracic spine and 10.6 mg/cm3higher at lumbar spine (95% CI, 5.1–16.1;P< 0.001). Among regular aspirin users, there was no association between drug use and trabecular BMD. Considering all spine fractures together, the prevalence ratio of fractures among aspirin users was 1.0 (95% CI, 0.6–1.6) and 1.1 (95% CI, 0.5–2.3) among COX-2–selective NSAID users.ConclusionsRegular use of aspirin has no significant association with trabecular BMD in either the thoracic or lumbar spine and no association with fracture prevalence. COX-2–selective NSAIDs may have modest positive association with BMD, but the mechanisms were not assessed and the observational study design makes residual confounding a possible alternate explanation. Potential pathological mechanisms warrant further longitudinal exploration.
Baseline Computed Tomography Radiomic and Genomic Assessment of Head and Neck Squamous Cell Carcinoma
Authors: Wang Colin Y. , Foy Joseph J. , Siewert Tanguy Y. , Haraf Daniel J. , Ginat Daniel T. 
Published: July 2020

Purpose
To determine the relationship between computed tomography (CT) radiomic features and gene expression levels in head and neck squamous cell carcinoma (HNSCC).

Methods
This retrospective study included 66 patients with HNSCC primary lesions (36 oropharyngeal, 6 hypopharyngeal, 10 laryngeal, 14 oral cavity). Gene expression information for 6 targetable genes (fibroblast growth factor receptor [FGFR]1, epidermal growth factor receptor [EGFR], FGFR2, FGFR3, EPHA2, PIK3CA) was obtained via Agilent microarrays from samples collected between 1997 and 2010. Pretreatment contrast-enhanced soft tissue neck CT scans were reviewed, and 142 radiomics features were derived. R was used to calculate Pearson correlation coefficients were calculated between gene expression levels and each radiomic feature. P values were adjusted using the false discovery rate (FDR) method.

Results
There were significant correlations between FGFR1 and 5 gray level cooccurrence matrix (GLCM) features with FDR-adjusted P values less than 0.05: inertia (r = 0.366, FDR-adjusted P = 0.006), absolute value (r = 0.31, FDR-adjusted P = 0.024), contrast (r = 0.366, FDR-adjusted P = 0.006), difference average (r = 0.31, FDR-adjusted P = 0.024), and difference variance (r = 0.37, FDR-adjusted P = 0.005). There was 1 correlated feature for FGFR2 with an FDR-adjusted P value less than 0.05: fractal dimension box-coarse (r = 0.33, FDR-adjusted P = 0.018). There was 1 correlated feature for EPHA2 with an FDR-adjusted P value less than 0.05: GLCM entropy (r = −0.28, FDR-adjusted P = 0.049). Six of the 7 features that showed significant correlation belonged to the GLCM class of features.

Conclusions
The CT radiomic features demonstrate correlations with FGFR1 status in HNSCC and should be further investigated for their potential to predict FGFR1 status.
Characterisation of aTeladorsagia circumcinctaglutathione transferase
Authors: Umair Saleh , Bouchet Charlotte L.G. , Deng Qing , Palevich Nikola , Simpson Heather V. 
Published: July 2020

ABSTRACTA 615 bp full length cDNA encoding aTeladorsagia circumcinctaglutathione transferase (TcGST) was cloned, expressed inEscherichia coliand the recombinant protein purified and its kinetic properties determined. The predicted protein consisted of 205 amino acids and was present as a single band of about 24 kDa on SDS-PAGE. Multiple alignments of the protein sequence ofTcGST with homologues from other helminths showed that the highest identity of 53-68% with haem-binding nematode proteins designated as members of the nu class of GSTs. Substrate binding sites and conserved regions were identified and were generally conserved. The predicted 3-dimensional structures ofTcGST andHcGST revealed highly open binding cavities typical of this class of GST, considered to allow greater accessibility to diverse ligands compared with other classes of GST. At 25 °C, the optimum pH forTcGST activity was pH 7, the Vmaxwas 1535 ± 33 nmoles.min-1.mg-1protein and the apparent Kmfor the substrate 1-chloro-2,4-dinitrobenzene (CDNB) was 0.22 ± 0.01 mM (mean ± SD, n = 2). Antibodies in both serum and saliva from field-immune, but not nematode-naÏve, sheep, recognised recombinantTcGST in enzyme-linked immunosorbent assays. The recognition of the recombinant protein by antibodies generated by exposure of sheep to the native enzyme indicates similar antigenicity of the two proteins. These findings could aid in the design of novel drugs and vaccine antigens for economically important parasites of livestock.
Effects of Tocilizumab in Critically Ill Patients With COVID-19: A Quasi-Experimental Study
Authors: Carvalho Victor , Turon Ricardo , Gonçalves Bruno , Ceotto Victor Fraga , Kurtz Pedro , Righy Cássia 
Published: July 2020

AbstractObjectivesCritically ill patients with COVID-19 may suffer from a cytokine release syndrome (CRS) characterized by remarkably high levels of interleukin 6 (IL-6). We assessed the effects of tocilizumab, an IL-6 receptor antagonist, on intra-hospital mortality and development of positive cultures in patients with COVID-19 admitted to the ICU.DesignPatients with COVID 19 admitted in the ICU who were treated with tocilizumab plus standard care were enrolled and compared to controls.SettingCOVID-19 severe diseasePatientsPatients with severe COVID-19 disease admitted in the ICU.InterventionsTocilizumab 400 mg IV two doses. Standard and intensive medical care as per institutional clinical protocol.Measures and Main ResultsMain outcome: 1) intra-hospital mortality; Secondary Outcomes: 1) the need for renal replacement therapy, 2) use of antibiotics and positive culture, and 3) inflammatory and oxygenation markers. There was no difference in mortality, need for renal replacement therapy, use of antibiotics or positive cultures between the two groups. The use of corticosteroids was more frequent in the treatment group. Levels of C-reactive protein (CRP) and WBC (white blood cells) counts declined significantly faster in the treatment group. Oxygenation markers rose significantly higher in patients in the tocilizumab group as compared to controls.ConclusionTocilizumab was associated with rapid improvement in oxygenation and a faster decrease of CRP and WBC counts in patients with COVID-19 and should be evaluated as rescue therapy for patients with progressive disease
Size Dependent Particle Removal Efficiency and Pressure Drop of a Dust Cleaning Material For Use as Facemask Filters for Protection during COVID-19
Authors: Dhanraj David , Choudhary Shruti , Raven Pat , Biswas Pratim 
Published: July 2020

AbstractCOVID-19 pandemic has caused a severe demand for facemasks, and this has resulted in the use of those made from alternate media. As SARS-CoV-2 spreads primarily due to airborne droplets, it is critical to verify the filtration efficiency of these alternate media based facemasks. While several media are being tested and used, commercially available dust cleaners have shown reasonable filtration efficiency. This may also be due to the potential electrostatic charge on the surface which enhances capture of the fine particles. In this manuscript, we report the size dependent filtration efficiency studied systematically in a filter holder-based system as 47 mm punches; and test results on a mannequin that was 3D printed wearing a bandana mask that was placed in a chamber.
A Quantitative Lung Computed Tomography Image Feature for Multi-Center Severity Assessment of COVID-19
Authors: Ghosh Biswajoy , Kumar Nikhil , Sadhu Anup K. , Ghosh Nirmalya , Mitra Pabitra , Chatterjee Jyotirmoy 
Published: July 2020

AbstractThe COVID-19 pandemic has affected millions and congested healthcare systems globally. Hence an objective severity assessment is crucial in making therapeutic decisions judiciously. Computed Tomography (CT)-scans can provide demarcating features to identify severity of pneumonia —commonly associated with COVID-19—in the affected lungs. Here, a quantitative severity assessing chest CT image feature is demonstrated for COVID-19 patients. An open-source multi-center Italian database1 was used, among which 60 cases were incorporated in the study (age 27-86, 71% males) from 27 CT imaging centers. Lesions in the form of opacifications, crazy-paving patterns, and consolidations were segmented. The severity determining feature —Lnorm was quantified and established to be statistically distinct for the three —mild, moderate, and severe classes (p-value<0.0001). The thresholds of Lnorm for a 3-class classification were determined based on the optimum sensitivity/specificity combination from Receiver Operating Characteristic (ROC) analyses. The feature Lnorm classified the cases in the three severity categories with 86.88% accuracy. ‘Substantial’ to ‘almost-perfect’ intra-rater and inter-rater agreements were achieved involving expert and non-expert based evaluations (κ-score 0.79-0.97). We trained machine learning based classification models and showed Lnorm alone has a superior diagnostic accuracy over standard image intensity and texture features. Classification accuracy was further increased when Lnorm was used for 2-class classification i.e. to delineate the severe cases from non-severe ones with a high sensitivity (97.7%), and specificity (97.49%). Therefore, key highlights of this severity assessment feature are accuracy, lower dependency on expert availability, and wide utility across different imaging centers.
COVID-19 misinformation: mere harmless delusions or much more? A knowledge and attitude cross-sectional study among the general public residing in Jordan
Authors: Sallam Malik , Dababseh Deema , Yaseen Alaa’ , Al-Haidar Ayat , Taim Duaa , Eid Huda , Ababneh Nidaa A. , Bakri Faris G. , Mahafzah Azmi 
Published: July 2020

AbstractSince the emergence of the recent coronavirus disease 2019 (COVID-19) and its spread as a pandemic, media was teeming with misinformation that led to psychologic, social and economic consequences among the global public. Probing knowledge and anxiety regarding this novel infectious disease is necessary to identify gaps and sources of misinformation which can help public health efforts to design and implement more focused interventional measures. The aim of this study was to evaluate the knowledge, attitude and effects of misinformation about COVID-19 on anxiety level among the general public residing in Jordan. An online survey was used that targeted people aged 18 and above and residing in Jordan. The questionnaire included items on the following: demographic characteristics of the participants, knowledge about COVID-19, anxiety level and misconceptions regarding the origin of the pandemic. The total number of participants included in final analysis was 3150. The study population was predominantly females (76.0%), with mean age of 31 years. The overall knowledge of COVID-19 was satisfactory. Older age, male gender, lower monthly income and educational levels, smoking and history of chronic disease were associated with perceiving COVID-19 as a very dangerous disease. Variables that were associated with a higher anxiety level during the pandemic included: lower monthly income and educational level, residence outside the capital (Amman) and history of smoking. Misinformation about the origin of the pandemic (being part of a conspiracy, biologic warfare and the 5G networks role) was also associated with higher anxiety and lower knowledge about the disease. Social media platforms, TV and news releases were the most common sources of information about the pandemic. The study showed the potential harmful effects of misinformation on the general public and emphasized the need to meticulously deliver timely and accurate information about the pandemic to lessen the health, social and psychological impact of the disease.
Comparison of seroprevalence of SARS-CoV-2 infections with cumulative and imputed COVID-19 cases: systematic review
Authors: Byambasuren Oyungerel , Dobler Claudia C , Bell Katy , Rojas Diana Patricia , Clark Justin , McLaws Mary-Louise , Glasziou Paul 
Published: July 2020

AbstractBackgroundAccurate seroprevalence estimates of SARS-CoV-2 in different populations could clarify the extent to which current testing strategies are identifying all active infection, and hence the true magnitude and spread of the infection. Our primary objective was to identify valid seroprevalence studies of SARS-CoV-2 infection and compare their estimates with the reported, and imputed, COVID-19 case rates within the same population at the same time point.MethodsWe searched PubMed, Embase, the Cochrane COVID-19 trials, and Europe-PMC for published studies and pre-prints that reported anti-SARS-CoV-2 IgG, IgM and/or IgA antibodies for serosurveys of the general community from 1 Jan to 12 Aug 2020.ResultsOf the 2199 studies identified, 170 were assessed for full text and 17 studies representing 15 regions and 118,297 subjects were includable. The seroprevalence proportions in 8 studies ranged between 1%-10%, with 5 studies under 1%, and 4 over 10% - from the notably hard-hit regions of Gangelt, Germany; Northwest Iran; Buenos Aires, Argentina; and Stockholm, Sweden. For seropositive cases who were not previously identified as COVID-19 cases, the majority had prior COVID-like symptoms. The estimated seroprevalences ranged from 0.56-717 times greater than the number of reported cumulative cases – half of the studies reported greater than 10 times more SARS-CoV-2 infections than the cumulative number of cases.ConclusionsThe findings show SARS-CoV-2 seroprevalence is well below “herd immunity” in all countries studied. The estimated number of infections, however, were much greater than the number of reported cases and deaths in almost all locations. The majority of seropositive people reported prior COVID-like symptoms, suggesting that undertesting of symptomatic people may be causing a substantial under-ascertainment of SARS-CoV-2 infections.Key messagesSystematic assessment of 17-country data show SARS-CoV-2 seroprevalence is mostly less than 10% - levels well below “herd immunity”.High symptom rates in seropositive cases suggest undertesting of symptomatic people and could explain gaps between seroprevalence rates and reported cases.The estimated number of infections for majority of the studies ranged from 2-717 times greater than the number of reported cases in that region and up to 13 times greater than the cases imputed from number of reported deaths.
Peramivir, an anti-influenza virus drug, exhibits potential anti-cytokine storm effects
Authors: Zhang Chen-xi , Tu Ye , Kong De-pei , Li Yinghua , Chen Da-gui , Zhang Wan-nian , Su Li , Zhuang Chun-lin , Wang Zhi-bin 
Published: July 2020

AbstractCoronavirus Disease 2019 (COVID-19) infected by Severe Acute Respiratory Syndrome Coronavirus −2 (SARS-CoV-2) has been declared a public health emergency of international concerns. Cytokine storm syndrome (CSS) is a critical clinical symptom of severe COVID-19 patients, and the macrophage is recognized as the direct host cell of SARS-CoV-2 and potential drivers of CSS. In the present study, peramivir was identified to reduce TNF-α by partly intervention of NF-κB activity in LPS-induced macrophage model. In vivo, peramivir reduced the multi-cytokines in serum and bronchoalveolar lavage fluid (BALF), alleviated the acute lung injury and prolonged the survival time in mice. In human peripheral blood mononuclear cells (hPBMCs), peramivir could also inhibit the release of TNF-α. Collectively, we proposed that peramivir might be a candidate for the treatment of COVID-19 and other infections related CSS.Graphic Abstract
A glycoprotein mutation that emerged during the 2013-2016 Ebola virus epidemic alters proteolysis and accelerates membrane fusion
Authors: Fels J. Maximilian , Bortz Robert H. , Alkutkar Tanwee , Mittler Eva , Jangra Rohit K. , Spence Jennifer S. , Chandran Kartik 
Published: July 2020

AbstractGenomic surveillance of viral isolates during the 2013-2016 Ebola virus epidemic in Western Africa—the largest and most devastating filovirus outbreak on record—revealed several novel mutations. The responsible strain, named Makona, carries an A to V substitution at position 82 in the glycoprotein (GP), which is associated with enhanced infectivity in vitro. Here, we investigated the mechanistic basis for this enhancement, as well as the interplay between A82V and a T to I substitution at residue 544 of GP, which also modulates infectivity in cell culture. We found that both 82V and 544I destabilize GP with the residue at 544 impacting overall stability, while 82V specifically destabilizes proteolytically cleaved GP. Both residues also promote faster kinetics of lipid mixing of the viral and host membranes in live cells, individually and in tandem, which correlates with faster times to fusion following co-localization with the viral receptor Niemann-Pick C1 (NPC1). Further, GPs bearing 82V are more sensitive to proteolysis by cathepsin L (CatL), a key host factor for viral entry. Intriguingly, CatL processed 82V variant GPs to a novel product of ∼12K size, which we hypothesize corresponds to a form of GP more fully primed for fusion than previously detected. We thus propose a model in which 82V promotes more efficient GP processing by CatL, leading to faster viral fusion kinetics and higher infectivity.ImportanceThe 2013-2016 outbreak of Ebola virus disease in West Africa demonstrated the potential for previously localized outbreaks to turn into regional, or even global, health emergencies. With over 28,000 cases and 11,000 confirmed deaths, this outbreak was over 50 times as large as any previously recorded. This outbreak also afforded the largest ever collection of Ebola virus genomic sequence data, allowing new insights into viral transmission and evolution. Viral mutants arising during the outbreak have attracted attention for their potentially altered patterns of infectivity in cell culture, with potential, if unclear, implications for increased viral spread and/or virulence. Here, we report on the properties of one such mutation in the viral glycoprotein, A82V, and its interplay with a previously described polymorphism at position 544. We show that mutations at both residues promote infection and fusion activation in cells, but that A82V additionally leads to increased infectivity under cathepsin-limited conditions, and the generation of a novel glycoprotein cleavage product.
HiG2Vec: Hierarchical Representations of Gene Ontology and Genes in the Poincaré Ball
Authors: Kim Jaesik , Kim Dokyoon , Sohn Kyung-Ah 
Published: July 2020

AbstractKnowledge manipulation of gene ontology (GO) and gene ontology annotation (GOA) can be done primarily by using vector representation of GO terms and genes for versatile applications such as deep learning. Previous studies have represented GO terms and genes or gene products to measure their semantic similarity using the Word2Vec-based method, which is an embedding method to represent entities as numeric vectors in Euclidean space. However, this method has the limitation that embedding large graph-structured data in the Euclidean space cannot prevent a loss of information of latent hierarchies, thus precluding the semantics of GO and GOA from being captured optimally. In this paper, we propose hierarchical representations of GO and genes (HiG2Vec) that apply Poincaré embedding specialized in the representation of hierarchy through a two-step procedure: GO embedding and gene embedding. Through experiments, we show that our model represents the hierarchical structure better than other approaches and predicts the interaction of genes or gene products similar to or better than previous studies. The results indicate that HiG2Vec is superior to other methods in capturing the GO and gene semantics and in data utilization as well. It can be robustly applied to manipulate various biological knowledge.Availabilityhttps://github.com/JaesikKim/HiG2VecContactkasohn@ajou.ac.kr,Dokyoon.Kim@pennmedicine.upenn.edu
The neurokinin-1 receptor is expressed with gastrin-releasing peptide receptor in spinal interneurons and modulates itch
Authors: Sheahan Tayler D. , Warwick Charles A. , Fanien Louis G. , Ross Sarah E. 
Published: July 2020

AbstractThe neurokinin-1 receptor (NK1R, encoded byTacr1) is expressed in spinal dorsal horn neurons and has been suggested to mediate itch. However, previous studies relied heavily on neurotoxic ablation of NK1R spinal neurons, which limited further dissection of their function in spinal itch circuitry. Thus, we leveraged a newly developedTacr1CreERmouse line to characterize the role of NK1R spinal neurons in itch. We show that pharmacological activation of spinal NK1R and chemogenetic activation ofTacr1CreERspinal neurons increases itch behavior, whereas pharmacological inhibition of spinal NK1R suppresses itch behavior. We use fluorescencein situhybridization to characterize the endogenous expression ofTacr1throughout the superficial and deeper dorsal horn, as well as the lateral spinal nucleus.Retrograde labeling studies from the parabrachial nucleus show that less than 20% of superficialTacr1CreERdorsal horn neurons are spinal projection neurons, and thus the majority ofTacr1CreERare local interneurons. We then use a combination ofin situhybridization andex vivotwo-photon Ca2+imaging of the spinal cord to establish that NK1R and the gastrin-releasing peptide receptor (GRPR) are coexpressed within a subpopulation of excitatory superficial dorsal horn neurons. These findings are the first to describe a role for NK1R interneurons in itch and extend our understanding of the complexities of spinal itch circuitry.