bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crosstalk between microglia and patient-derived glioblastoma cells inhibit invasion in a three-dimensional gelatin hydrogel model
Authors: Chen Jee-Wei Emily , Lumibao Jan , Leary Sarah , Sarkaria Jann N. , Steelman Andrew J. , Gaskins H. Rex , Harley Brendan A. C. 
Published: August 2020

ABSTRACTBackgroundGlioblastoma is the most common and deadly form of primary brain cancer, accounting for more than thirteen thousand new diagnoses annually in the United States alone. Microglia are the innate immune cells within the central nervous system, acting as a front-line defense against injuries and inflammation via a process that involves transformation from a quiescent to an activated phenotype. Crosstalk between GBM cells and microglia represents an important axis to consider in the development of tissue engineering platforms to examine pathophysiological processes underlying GBM progression and therapy.MethodsThis work used a brain-mimetic hydrogel system to study patient-derived glioblastoma specimens and their interactions with microglia. Here, glioblastoma cells were either cultured alone in 3D hydrogels or in co-culture with microglia in a manner that allowed secretome-based signaling but prevented direct GBM-microglia contact. Patterns of GBM cell invasion were quantified using a three-dimensional spheroid assay. Secretome and transcriptome (via RNAseq) were used to profile the consequences of GBM-microglia interactions.ResultsMicroglia displayed an activated phenotype as a result of GBM crosstalk. Three-dimensional migration patterns of patient derived glioblastoma cells showed invasion was significantly decreased in response to microglia paracrine signaling. Potential molecular mechanisms underlying with this phenotype were identified from bioinformatic analysis of secretome and RNAseq data.ConclusionThe data demonstrate a tissue engineered hydrogel platform can be used to investigate crosstalk between immune cells of the tumor microenvironment related to GBM progression. Such multidimensional models may provide valuable insight to inform therapeutic innovations to improve GBM treatment.
Severe COVID-19 and Diabetes - A Retrospective Cohort Study from Three London Teaching Hospitals
Authors: Izzi-Engbeaya Chioma , Distaso Walter , Amin Anjali , Yang Wei , Idowu Oluwagbemiga , Kenkre Julia S , Shah Ronak J , Woin Evelina , Shi Christine , Alavi Nael , Bedri Hala , Brady Niamh , Blackburn Sophie , Leczycka Martina , Patel Sanya , Sokol Elizaveta , Toke-Bjolgerud Edward , Qayum Ambreen , Abdel-Malek Mariana , Hope David C D , Oliver Nick S , Bravis Vasiliki , Misra Shivani , Tan Tricia M , Hill Neil , Salem Victoria 
Published: August 2020

ABSTRACTPatients with diabetes mellitus admitted to hospital with COVID-19 caused by infection with the novel coronavirus (SARS-CoV-2) have poorer outcomes. However, the drivers for this are not fully elucidated. We performed a retrospective cohort study, including detailed pre-hospital and presenting clinical and biochemical factors of 889 patients diagnosed with COVID-19 in three constituent hospitals of a large London NHS Trust. 62% of patients with severe COVID-19 were of non-White ethnic backgrounds and the prevalence of diabetes was 38%. 323 (36%) patients met the primary outcome of death or admission to the intensive care unit (ICU) within 30 days of diagnosis. Male gender, advancing age and the Clinical Frailty Scale, an established measure of multimorbidity, independently predicted poor outcomes on multivariate analysis. Diabetes did not confer an independent risk for adverse outcomes in COVID-19, although patients with diabetes and ischaemic heart disease were at particular risk. Additional risk factors which significantly and independently associated with poorer outcomes in patients with diabetes were age, male gender and lower platelet count. Antiplatelet medication was associated with a lower risk of death/ICU admission and should be evaluated in randomised clinical trials amongst high risk patient groups.
Bone health risk assessment in a clinical setting: an evaluation of a new screening tool for active populations
Authors: Keay Nicola , Francis Gavin , Hind Karen 
Published: August 2020

AbstractIntroductionRisk factors for poor bone health are not restricted to older, sedentary populations for whom current screening is focused. Furthermore, access to dual X-ray absorptiometry scanning can be limited in clinical practice. The purpose of the current study was to develop a bone health-screening tool suitable for inclusion of both younger and active populations, combined with radiofrequency echographic multi spectrometry technology (REMS).Methodology88 participants attending a physiotherapy clinic in the UK were recruited to the study: 71 women (mean age 41.5 SD 14.0 years); 17 men (mean age 40.2 SD 14.9 years). Participants completed an online bone health-screening questionnaire developed specifically for this study covering a range of lifestyle, physiological factors, combined with medical interview and received bone mineral density (BMD) measurement at the lumbar spine and femoral neck using REMS.ResultsScoring of the bone health-screening questionnaire produced a distribution of bone health scores, with lower scores suggesting a higher risk for poor bone health. In women, scores ranged from -10 to +12, mean score 2.2 (SD 4.8). In men, scores ranged from 0 to 12, mean score 6.9 (SD 3.2). A positive correlation was observed between the bone health score derived from the questionnaire and lumbar spine and femoral neck BMD Z-scores (p<0.01).ConclusionsThis new and comprehensive bone health-screening questionnaire with interview was effective in identifying active individuals at risk of bone fragility, who might be missed by current screening methods. The use of REMS technology to measure bone health, was feasible in the clinical setting.
Model-based projections for COVID-19 outbreak size and student-days lost to closure in Ontario childcare centers and primary schools
Authors: Phillips Brendon , Browne Dillon T. , Anand Madhur , Bauch Chris T. 
Published: August 2020

ABSTRACTThere is a pressing need for evidence-based scrutiny of plans to re-open childcare during the COVID-19 pandemic. Here we developed an agent-based model of SARS-CoV-2 transmission within a childcare center and households. Scenarios varied the student-to-educator ratio (15:2, 8:2, 7:3), and family clustering (siblings together vs. random assignment). We also evaluated a primary school setting (30:1, 15:1 and 8:1) including cohorts that alternate weekly. In the childcare scenarios, grouping siblings significantly reduced outbreak size and student-days lost. We identify an intensification cascade specific to classroom outbreaks of respiratory viruses with presymptomatic infection. In both childcare and primary school settings, each doubling of class size from 8 to 15 to 30 more than doubled the outbreak size and student-days lost, by factors of 2-5, respectively 2.5-4.5, depending on the scenario. Proposals for childcare and primary school reopening could be enhanced for safety by switching to lower ratios and sibling groupings.
Comparison of the Safety and Immunogenicity of a Novel Matrix-M-adjuvanted Nanoparticle Influenza Vaccine with a Quadrivalent Seasonal Influenza Vaccine in Older Adults: A Randomized Controlled Trial
Authors: Shinde Vivek , Cho Iksung , Plested Joyce S. , Agrawal Sapeckshita , Fiske Jamie , Cai Rongman , Zhou Haixia , Pham Xuan , Zhu Mingzhu , Cloney-Clark Shane , Wang Nan , Zhou Bin , Lewis Maggie , Price-Abbott Patty , Patel Nita , Massare Michael J , Smith Gale , Keech Cheryl , Fries Louis , Glenn Gregory M 
Published: August 2020

ABSTRACTBackgroundImproved seasonal influenza vaccines for older adults are urgently needed, which can induce broadly cross-reactive antibodies and enhanced T-cell responses, particularly against A(H3N2) viruses, while avoiding egg-adaptive antigenic changes.MethodsWe randomized 2654 clinically-stable, community-dwelling adults ≥65 years of age 1:1 to receive a single intramuscular dose of either Matrix-M-adjuvanted quadrivalent nanoparticle influenza vaccine (qNIV) or a licensed inactivated influenza vaccine (IIV4) in this randomized, observer-blinded, active-comparator controlled trial conducted during the 2019-2020 influenza season. The primary objectives were to demonstrate the non-inferior immunogenicity of qNIV relative to IIV4 against 4 vaccine-homologous strains, based on Day 28 hemagglutination-inhibiting (HAI) antibody responses, described as geometric mean titers and seroconversion rate difference between treatment groups, and to describe the safety of qNIV. Cell-mediated immune (CMI) responses were measured by intracellular cytokine analysis.FindingsqNIV demonstrated immunologic non-inferiority to IIV4 against 4 vaccine-homologous strains as assessed by egg-based HAI antibody responses. Corresponding wild-type HAI antibody responses by qNIV were significantly higher than IIV4 against all 4 vaccine-homologous strains (22-66% increased) and against 6 heterologous A(H3N2) strains (34-46% increased), representing multiple genetically and/or antigenically distinct clades/subclades (all p-values <0.001). qNIV induced 3.·1- to 3·9- and 4·0- to 4·9-fold increases in various polyfunctional phenotypes of antigen-specific effector CD4+ T-cells against A(H3N2) and B/Victoria strains at Day 7 post-vaccination, respectively, while corresponding fold-rises induced by IIV4 at Day 7 were 1·3-1·4 and 1·7-2·0; representing a 126-189% improvement in CMI responses for qNIV (all p-values <0·001). Local reactogenicity, primarily mild to moderate and transient pain, was higher in the qNIV group.InterpretationqNIV was well tolerated and produced a qualitatively and quantitatively enhanced humoral and cellular immune response in older adults. These enhancements may be critical to improving the effectiveness of currently licensed influenza vaccines.FundingNovavax.
Iranian Dental Students and Specialists’ Knowledge and Attitude about Obstructive Sleep Apnea
Authors: Shafiee Shervin , Sofi-Mahmudi Ahmad , Behnaz Mohammad , Safiaghdam Hannaneh , Sadr Soroush 
Published: August 2020

AbstractIntroductionObstructive sleep apnea is a relatively common sleep disorder, which leads to multiple sleep arousal and hypoxemia. It also has a significant socioeconomic impact. Dentists can have a role in screening as well as treating apnea by orthodontic devices. No study has evaluated the knowledge and attitude of dental health professionals about obstructive sleep apnea (OSA) in Iran. We aimed to measure knowledge and attitude among students and faculty members of Shahid Beheshti Dental School, Tehran, Iran about OSA.Materials and MethodsWe conducted a cross-sectional survey among residents and professors in oral and maxillofacial surgery, orthodontics, and oral medicine specialties and dental students. The Obstructive Sleep Apnea Knowledge and Attitude (OSAKA) questionnaire was used to obtain the information regarding knowledge and attitude. We used Chi-square, Kruskall Wallis, Mann-Whitney U test for statistical analysis. The data were analyzed by SPSS 22.0 and a p-value lower than 0.05 considered to be significant.ResultsOne hundred ninety-seven participants, including 43 dental students, 68 dental residents, and 64 dental professors filled the survey. Mean knowledge score among all participants was 10.69±3.133. Overall, oral medicine and oral and maxillofacial surgery professors had significantly higher correct answer ratios in the knowledge section than fifth and sixth-year dental students (p<0.001). There was no significant difference among other groups (p>0.05). About attitude, 91% of respondents reported that OSA is an important or extremely important disorder. However, only 10.2% and 16.9% felt confident about the ability to manage patients with OSA and identifying patients at risk for OSA, respectively.ConclusionAll of the participants had poor knowledge but a positive attitude towards OSA. This shows the necessity of better education about OSA.
Petabase-scale sequence alignment catalyses viral discovery
Authors: Edgar Robert C. , Taylor Jeff , Lin Victor , Altman Tomer , Barbera Pierre , Meleshko Dmitry , Lohr Dan , Novakovsky Gherman , Buchfink Benjamin , Al-Shayeb Basem , Banfield Jillian F. , de la Peña Marcos , Korobeynikov Anton , Chikhi Rayan , Babaian Artem 
Published: August 2020

AbstractPublic databases contain a planetary collection of nucleic acid sequences, but their systematic exploration has been inhibited by a lack of efficient methods for searching this corpus, now exceeding multiple petabases and growing exponentially [1, 2]. We developed a cloud computing infrastructure,Serratus, to enable ultra-high throughput sequence alignment at the petabase scale. We searched 5.7 million biologically diverse samples (10.2 petabases) for the hallmark gene RNA dependent RNA polymerase, identifying well over 105novel RNA viruses and thereby expanding the number of known species by roughly an order of magnitude. We characterised novel viruses related to coronaviruses and to hepatitisδvirus, respectively and explored their environmental reservoirs. To catalyse a new era of viral discovery, we established a free and comprehensive database of these data and tools. Expanding the known sequence diversity of viruses can reveal the evolutionary origins of emerging pathogens and improve pathogen surveillance for the anticipation and mitigation of future pandemics.
Sofosbuvir Terminated RNA is More Resistant to SARS-CoV-2 Proofreader than RNA Terminated by Remdesivir
Authors: Jockusch Steffen , Tao Chuanjuan , Li Xiaoxu , Chien Minchen , Kumar Shiv , Morozova Irina , Kalachikov Sergey , Russo James J. , Ju Jingyue 
Published: August 2020

AbstractSARS-CoV-2 is responsible for COVID-19, resulting in the largest pandemic in over a hundred years. After examining the molecular structures and activities of hepatitis C viral inhibitors and comparing hepatitis C virus and coronavirus replication, we previously postulated that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) might inhibit SARS-CoV-2.1 We subsequently demonstrated that Sofosbuvir triphosphate is incorporated by the relatively low fidelity SARS-CoV and SARS-CoV-2 RNA-dependent RNA polymerases (RdRps), serving as an immediate polymerase reaction terminator, but not by a host-like high fidelity DNA polymerase.2,3 Other investigators have since demonstrated the ability of Sofosbuvir to inhibit SARS-CoV-2 replication in lung and brain cells;4,5 additionally, COVID-19 clinical trials with EPCLUSA6 and with Sofosbuvir plus Daclatasvir7 have been initiated in several countries. SARS-CoV-2 has an exonuclease-based proofreader to maintain the viral genome integrity.8 Any effective antiviral targeting the SARS-CoV-2 RdRp must display a certain level of resistance to this proofreading activity. We report here that Sofosbuvir terminated RNA resists removal by the exonuclease to a substantially higher extent than RNA terminated by Remdesivir, another drug being used as a COVID-19 therapeutic. These results offer a molecular basis supporting the current use of Sofosbuvir in combination with other drugs in COVID-19 clinical trials.
Time-to-Event Modeling of Hypertension Reveals the Nonexistence of True Controls
Authors: Shriner Daniel , Bentley Amy R. , Zhou Jie , Ekoru Kenneth , Doumatey Ayo P. , Chen Guanjie , Adeyemo Adebowale , Rotimi Charles N. 
Published: August 2020

AbstractGiven a lifetime risk of ~90% by the ninth decade of life, it is unknown if there are true controls for hypertension in epidemiological and genetic studies. Here, we use the Bayesian framework to compare logistic and time-to-event approaches to modeling hypertension. Using a proportional hazards model, we explored nonparametric and parametric models of the baseline hazard function, accounting for interval censoring. In the Howard University Family Study (HUFS), a population-based study of African Americans from Washington, D.C., the median age at hypertension was 48 years, baseline hazard rates increased with age until 55 years, and the probability of being free of hypertension at 85 years of age was 12.2%. In the nationwide NHANES study, the median age at hypertension was 42 years in African Americans, in contrast to 57 years in European Americans and 56 years in Mexican Americans. Baseline hazard rates increased with age until 58 years in African Americans, comparable to 60 years in European Americans and 58 years in Mexican Americans. The probability of being free of hypertension at 85 years of age was 8.4% in African Americans, in contrast to 21.4% in European Americans and 20.6% in Mexican Americans. In all four groups, baseline hazard rates decreased but did not reach zero, consistent with the nonexistence of controls. Model fits were comparable for a proportional hazards model based on gamma-distributed hazard rates under a correlated prior process and a logistic model adjusted for age and age2. Last, using an agnostic model screening approach of 38 potential covariates, we identified and replicated in all groups a model that included chloride, low-density lipoprotein cholesterol, uric acid, and weight. With age and age2, the variance explained by these covariates was 40.9% in African Americans, 34.8% in European Americans, and 28.3% in Mexican Americans. Taken together, modeling of the baseline hazard function of hypertension suggests that there are no true controls and that controls in logistic regression are cases with a late age of onset. These findings shed considerable insights into the design of genetic and epidemiological studies of hypertension with implications for ethnic health disparities.
Relationship between dietary choline intake and diabetes mellitus in the National Health and Nutrition Examination Survey 2007-2010
Authors: Zhou Long , Li Xiang , Li Shuhong , Wen Xiaoxiao , Peng Yaguang , Zhao Liancheng 
Published: August 2020

ABSTRACTBackgroundPrevious studies have shown that elevated trimethylamine N-oxide (TMAO) was associated with a higher risk of diabetes mellitus (DM). Little is known about the relationship between dietary intake of choline, which is a major dietary precursor for gut microbiome-derived TMAO, and DM in the general population.ObjectiveThe present study aims to explore the relationship between dietary choline intakes and DM in the United States (US) adult population.DesignCross-sectional data were derived from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 of 8621 individuals aged 20 years or older. Multivariable logistic regression models were used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for DM of each quartile category of energy-adjusted choline intakes. The restricted cubic spline model was used for the dose-response analysis. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of choline intake for predicting DM.ResultsA linear dose-response relationship between dietary choline intakes and the odds of DM was found after adjustment for multiple potential confounding factors, p for linear =0.0002. With the lowest quartile category of choline as the reference, the multivariable-adjusted ORs and 95% CIs of the second, third, and highest quartile categories were 1.22 (0.98, 1.52), 1.26 (1.01, 1.56), and 1.42 (1.15, 1.77), respectively, p for trend =0.0024. Per 100 mg/d increase in energy-adjusted choline resulted in 15% (95% CI: 7%, 22%) higher odds of DM. The ROC analysis identified an energy-adjusted choline of 331.7 mg/d as the optimal cut-off value for predicting DM, with 52.5% sensitivity and 60.7% specificity.ConclusionThis study supports a positive and linear relationship between dietary choline intake and DM in the US adult population. Further studies are warranted to replicate our findings in other populations and elucidate the potential mechanisms.
Sensitivity, specificity and predictive values of molecular and serological tests for COVID-19
Authors: Bisoffi Zeno , Pomari Elena , Deiana Michela , Piubelli Chiara , Ronzoni Niccolò , Beltrame Anna , Bertoli Giulia , Riccardi Niccolò , Perandin Francesca , Formenti Fabio , Gobbi Federico , Buonfrate Dora , Silva Ronaldo 
Published: August 2020

ABSTRACTAccuracy of diagnostic tests is essential for suspected cases of Coronavirus Disease 2019 (COVID-19). This study aimed to assess the sensitivity, specificity and positive and negative predictive value (PPV and NPV) of molecular and serological tests for the diagnosis of SARS-CoV-2 infection. A total of 346 consenting, adult patients were enrolled at the emergency room of IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy. We evaluated three RT-PCR methods including six different gene targets; five serologic rapid diagnostic tests (RDT); one ELISA test. The final classification of infected/not infected patients was performed using Latent Class Analysis in combination with clinical re-assessment of incongruous cases and was the basis for the main analysis of accuracy.Of 346 patients consecutively enrolled, 85 (24.6%) were classified as infected. The molecular test with the highest sensitivity, specificity, PPV and NPV was RQ-SARS-nCoV-2 with 91.8% (C.I. 83.8-96.6), 100% (C.I. 98.6-100.0), 100.0% (C.I. 95.4-100.0) and 97.4% (C.I. 94.7-98.9) respectively, followed by CDC 2019-nCoV with 76.2% (C.I. 65.7-84.8), 99.6% (C.I. 97.9-100.0), 98.5% (C.I. 91.7-100.0) and 92.9% (C.I. 89.2-95.6) and by in-house test targeting E-RdRp with 61.2% (C.I. 50.0-71.6), 99.6% (C.I. 97.9-100.0), 98.1% (C.I. 89.9-100.0) and 88.7% (C.I. 84.6-92.1). The analyses on single gene targets found the highest sensitivity for S and RdRp of the RQ-SARS-nCoV-2 (both with sensitivity 94.1%, C.I. 86.8-98.1). The in-house RdRp had the lowest sensitivity (62.4%, C.I. 51.2-72.6). The specificity ranged from 99.2% (C.I. 97.3-99.9) for in-house RdRp and N2 to 95.0% (C.I. 91.6-97.3) for E. The PPV ranged from 97.1% (C.I. 89.8-99.6) of N2 to 85.4% (C.I. 76.3-92.00) of E, and the NPV from 98.1% (C.I. 95.5-99.4) of gene S to 89.0% (C.I. 84.8-92.4) of in-house RdRp. All serological tests had <50% sensitivity and low PPV and NPV. One RDT (VivaDiag IgM) had high specificity (98.5%, with PPV 84.0%), but poor sensitivity (24.7%). Molecular tests for SARS-CoV-2 infection showed excellent specificity, but significant differences in sensitivity. As expected, serological tests have limited utility in a clinical context.