bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-site clinical validation of Isothermal Amplification based SARS-COV-2 detection assays using different sampling strategies
Authors: Desai Kanan T. , Alfaro Karla , Mendoza Laura , Faron Matthew , Mesich Brian , Maza Mauricio , Dominguez Rhina , Valenzuela Adriana , DÍaz Acosta Chyntia , MartÍnez Magaly , Felix Juan C. , Masch Rachel , Gabrilovich Sofia , Plump Michael , Novetsky Akiva P. , Einstein Mark H. , Douglas Nataki C. , Cremer Miriam , Wentzensen Nicolas 
Published: July 2021

AbstractBackgroundIsothermal amplification-based tests were developed as rapid, low-cost, and simple alternatives to real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-COV-2 detection.MethodsClinical performance of two isothermal amplification-based tests (Atila Biosystems iAMP COVID-19 detection test and OptiGene COVID-19 Direct Plus RT-LAMP test) was compared to clinical RT-PCR assays using different sampling strategies. A total of 1378 participants were tested across four study sites.ResultsCompared to standard of care RT-PCR testing, the overall sensitivity and specificity of the Atila iAMP test for detection of SARS-CoV-2 were 76.2% and 94.9%, respectively, and increased to 88.8% and 89.5%, respectively, after exclusion of an outlier study site. Sensitivity varied based on the anatomic collected site. Sensitivity for nasopharyngeal was 65.4% (range across study sites:52.8%-79.8%), mid-turbinate 88.2%, saliva 55.1% (range across study sites:42.9%-77.8%) and anterior nares 66.7% (range across study sites:63.6%-76.5%). The specificity for these anatomic collection sites ranged from 96.7% to 100%. Sensitivity improved in symptomatic patients (overall 82.7%) and those with a higher viral load (overall 92.4% for ct≤25). Sensitivity and specificity of the OptiGene Direct Plus RT-LAMP test, conducted at a single study-site, were 25.5% and 100%, respectively.ConclusionsThe Atila iAMP COVID test with mid-turbinate sampling is a rapid, low-cost assay for detecting SARS-COV-2, especially in symptomatic patients and those with a high viral load, and could be used to reduce the risk of SARS-COV-2 transmission in clinical settings. Variation of performance between study sites highlights the need for site-specific clinical validation of these assays before clinical adoption.
Colorectal Cancer Disparities Across the Continuum of Cancer Care: A Systematic Review and Meta-Analysis
Authors: Syvyk Solomiya , Roberts Sanford E. , Finn Caitlin B. , Wirtalla Chris , Kelz Rachel 
Published: July 2021

Structured AbstractBackground and ObjectivesDisparate colorectal cancer outcomes persist in vulnerable populations. We aimed to examine the distribution of research across the colorectal cancer care continuum, and to determine disparities in the use of Surgery among Black patients.MethodsA systematic review and meta-analysis of colorectal cancer disparities studies was performed. The meta-analysis assessed three utilization measures in Surgery.ResultsOf 1,199 publications, 60% focused on Prevention, Screening, or Diagnosis, 20% on Survivorship, 15% on Treatment, and 1% on End-of-Life Care. A total of 16 studies, including 1,110,674 patients, were applied to three separate meta-analyses regarding utilization of Surgery. Black colorectal cancer patients were less likely to receive surgery, twice as likely to refuse surgery, and less likely to receive laparoscopic surgery when compared to White patients.ConclusionsOver the past 10 years, the majority of published research remained focused on the prevention, screening, or diagnosis domain. Given the observed treatment disparities and persistently elevated disease-specific mortality among Black patients, future efforts to reduce colorectal cancer disparities should include interventions within Surgery.SynopsisIn this systematic review on disparities along the colorectal cancer care continuum, we found that 64% of research has been focused on prevention, screening, or diagnosis while only 6% addressed surgical disparities. In the meta-analysis, Black patients were less likely to undergo surgery, more likely to refuse surgery, and less likely to undergo laparoscopic surgery, when compared to White patients. Future research should target treatment differences across populations in order to impact persistent disparities in colorectal cancer survival.
The toll of COVID-19 on African children: A descriptive analysis on the COVID-19-related morbidity and mortality among the pediatric population in Sub-Saharan Africa
Authors: Velásquez Sabina Rodriguez , Jacques Léa , Dalal Jyoti , Sestito Paolo , Habibi Zahra , Venkatasubramanian Akarsh , Nguimbis Benedict , Mesa Sara Botero , Chimbetete Cleophas , Keiser Olivia , Impouma Benido , Mboussou Franck , William George Sie , Ngoy Nsenga , Talisuna Ambrose , Gueye Abdou Salam , Hofer Cristina Barroso , Cabore Joseph Waogodo 
Published: July 2021

AbstractIntroductionSince the beginning of the COVID-19 pandemic, very little data on the epidemiological characteristics among the pediatric population in Africa has been published. This paper examines the age and sex distribution of the morbidity and mortality rate in children with COVID-19 and compares it to the adult population within 15 Sub-Saharan African countries.MethodsA merge line listing dataset using a reverse engineering model shared by countries within the Regional Office for Africa was analyzed. Patients diagnosed within 1 March 2020 and 1 September 2020 with confirmed positive RT-PCR test for SARS-CoV-2 were analyzed. Children’s data were stratified into three age groups: 0-4 years, 5-11 years, and 12-17 years, while adults were combined. The cumulative incidence of cases including its medians and 95% confidence intervals were calculated.Results9% of the total confirmed cases and 2.4% of the reported deaths were pediatric cases. The 12-17 age group in all 15 countries showed the highest cumulative incidence proportion in children. COVID-19 cases in males and females under the age of 18 were evenly distributed. Among adults, a higher case incidence per 100,000 people was observed compared to children.ConclusionThe cases and deaths within the children’s population was smaller than the adult population. These differences can reflect biases in COVID-19 testing protocols and reporting implemented by countries, highlighting the need for more extensive investigation and focus on the effects of COVID-19 in children.
Whole-genome sequencing of SARS-COV-2 showed wide spread of B.1.525 in February 2021 in Libya
Authors: Alhudiri Inas M , Ramadan Ahmad M. , Ibrahim Khaled M , Abdalla Adel , Eljilani Mouna , Salem Mohamed Ali , Elgheriani Hajer Mohamed , El Meshri Salah Edin , Elzagheid Adam 
Published: July 2021

AbstractAlpha (B.1.1.7) SARS-COV-2 variant was detected in September 2020 in minks and humans in Denmark and UK. This variant has several mutations in the spike region (S) which could increase the transmissibility of the virus 43-90% over previously circulating variants. The National Center for Disease Control (NCDC) announced on 24th February 2021 a 25% frequency of B.1.1.7 strain in Libya using a reverse-transcriptase quantitative PCR assay. This assay relies on the specific identification of the H69-V70 deletion in S gene which causes its failure of amplification (SGTF). This deletion is not specific for B.1.1.7; but is also characteristic of two other SARS-COV-2 variants. This study aimed to estimate the frequency of B.1.1.7 and identify other variants circulating in Libya in February 2021. We performed whole genome sequencing of 67 positive SARS-COV-2 samples collected on 25th February 2021 in Libya which were also tested by RT-qPCR for SGTF. Our results showed that 55% of samples had mutations specific to B.1.525 strain and only ∼3% of samples belonged to B.1.1.7. These findings suggested that B.1.525 was spreading widely in Libya. The use of such RT-qPCR assay although useful to track some variants, it cannot discriminate between variants with H69-V70 deletion. RT-qPCR assays could be multiplexed to identify multiple variants and screen samples prior to sequencing. We emphasize on the need for providing whole-genome sequencing to the main COVID-19 diagnostic laboratories in Libya as well as establishing international collaboration for building capacity and advancing research in this time of the pandemic.
Increased Histone-DNA Complexes and Endothelial-Dependent Thrombin Generation in Severe COVID-19
Authors: Bouchard Beth A. , Colovos Christos , Lawson Michael , Osborn Zachary , Sackheim Adrian , Mould Kara J. , Janssen William J. , Cohen Mitchell J. , Majumdar Devdoot , Freeman Kalev 
Published: July 2021

ABSTRACTObjectiveCoagulopathy in severe COVID-19 is common but poorly understood. The purpose of this study was to determine how SARS-CoV-2 infection impacts histone levels, fibrin structure, and endogenous thrombin potential in the presence and absence of endothelial cells.ApproachWe studied individuals with SARS-CoV-2 infection and acute respiratory distress syndrome at the time of initiation of mechanical ventilation compared to healthy controls. Blood samples were assayed for levels of histone-DNA complexes. Confocal microscopy was used to evaluate fibrin structure in clots formed from recalcified plasma samples using fluorescently-labeled fibrinogen. Endogenous thrombin potential was measured by calibrated automated thrombin assays in the presence of tissue factor and phospholipid (PCPS) or cultured human endothelial cells.ResultsCirculating nucleosomes were elevated in the plasma of COVID-19 patients relative to healthy controls (n=6, each group). COVID-19 patient plasma thrombin generation was also altered. Despite having an increased endogenous thrombin potential, patient plasma samples exhibited prolonged lag times and times to peak thrombin in the presence of added tissue factor and PCPS. Strikingly different results were observed when endothelial cells were used in place of tissue factor and PCPS. Control plasma samples did not generate measurable thrombin (lag time >60 min); in contrast, plasma samples from COVID-19+ patients generated thrombin (mean lag time ∼20 min). Consistent with the observed alterations in thrombin generation, clots from COVID-19 subjects exhibited a denser fibrin network, thinner fibers and lower fibrin resolvability.ConclusionsElevated histones, aberrant fibrin formation, and increased endothelial-dependent thrombin generation in COVID-19 may contribute to coagulopathy.HIGHLIGHTSHistone-DNA complexes are significantly elevated in the plasma of patients with severe SARS-CoV-2 infection.Measures of thrombin generation by calibrated automated thrombography and fibrin clots formedin situare altered in severe COVID-19.Plasma from COVID-19 patients promotes thrombin generation on cultured endothelial cells in the absence of added tissue factor or phospholipids.The additive effects of histones on thrombin generation and endothelial cell function may play a major role in the thrombotic complications observed in severe SARS-CoV-2 infection.
Noradrenergic deficits contribute to apathy in Parkinson’s disease through the precision of expected outcomes
Authors: Hezemans Frank H. , Wolpe Noham , O’Callaghan Claire , Ye Rong , Rua Catarina , Jones P. Simon , Murley Alexander G. , Holland Negin , Regenthal Ralf , Tsvetanov Kamen A. , Barker Roger A. , Williams-Gray Caroline H. , Robbins Trevor W. , Passamonti Luca , Rowe James B. 
Published: July 2021

AbstractApathy is a debilitating feature of many diseases, including Parkinson’s disease. We tested the hypothesis that degeneration of the locus coeruleus-noradrenaline system contributes to apathy by modulating the relative weighting of prior beliefs about action outcomes. Participants with mild-to-moderate idiopathic Parkinson’s disease (N=17) completed a double-blind, placebo-controlled, crossover study with 40 mg of the noradrenaline reuptake inhibitor atomoxetine. Prior weighting was inferred from psychophysical analysis of performance in an effort-based visuomotor task, and was confirmed as negatively correlated with apathy. Locus coeruleus integrity was assessed in vivo using magnetisation transfer imaging at 7T. The effect of atomoxetine depended on locus coeruleus integrity: participants with a more degenerate locus coeruleus showed a greater increase in prior weighting on atomoxetine versus placebo. The results indicate a contribution of the noradrenergic system to apathy and potential benefit from noradrenergic treatment of people with Parkinson’s disease, subject to stratification according to locus coeruleus integrity.
SARS-CoV-2 environmental contamination from hospitalised COVID-19 patients receiving aerosol generating procedures
Authors: Winslow RL , Zhou J , Windle EF , Nur I , Lall R , Ji C , Millar JE , Dark P , Naisbitt J , Simonds A , Dunning J , Barclay W , Baillie K , Perkins GD , Semple MG , McAuley DF , Green CA 
Published: July 2021

ABSTRACTBackgroundContinuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered ‘aerosol-generating procedures’ (AGPs) in the treatment of COVID-19. We aimed to measure air and surface environmental contamination of SARS-CoV-2 virus when CPAP and HFNO were used, compared with supplemental oxygen, to investigate the potential risks of viral transmission to healthcare workers and patients.Methods30 hospitalised patients with COVID-19 requiring supplemental oxygen, with a fraction of inspired oxygen ≥0.4 to maintain oxygen saturations ≥94%, were prospectively enrolled into an observational environmental sampling study. Participants received either supplemental oxygen, CPAP or HFNO (n=10 in each group). A nasopharyngeal swab, three air and three surface samples were collected from each participant and the clinical environment. RT qPCR analyses were performed for viral and human RNA, and positive/suspected-positive samples were cultured for the presence of biologically viable virus.ResultsOverall 21/30 (70%) of participants tested positive for SARS-CoV-2 RNA in the nasopharynx. In contrast, only 4/90 (4%) and 6/90 (7%) of all air and surface samples tested positive (positive for E and ORF1a) for viral RNA respectively, although there were an additional 10 suspected-positive samples in both air and surfaces samples (positive for E or ORF1a). CPAP/HFNO use or coughing was not associated with significantly more environmental contamination. Only one nasopharyngeal sample was culture positive.ConclusionsThe use of CPAP and HFNO to treat moderate/severe COVID-19 was not associated with significantly higher levels of air or surface viral contamination in the immediate care environment.
Maternal plasma lipids are involved in the pathogenesis of preterm birth
Authors: Chen Yile , He Bing , Liu Yu , Aung Max T. , Rosario-Pabón Zaira , Vélez-Vega Carmen M. , Alshawabkeh Akram , Cordero José F. , Meeker John D. , Garmire Lana X. 
Published: July 2021

AbstractBackgroundPreterm birth is defined by the onset of labor at a gestational age shorter than 37 weeks and it can lead to premature birth and impose a threat to newborns’ health. The Puerto Rico PROTECT cohort is a well-characterized prospective birth cohort that was designed to investigate environmental and social contributors to preterm birth in Puerto Rico, where preterm birth rates have been elevated in recent decades. To elucidate possible relationships between metabolites and preterm birth in this cohort, we conducted a nested case-control study to conduct untargeted metabolomic characterization of maternal plasma of 31 preterm birth women and 69 full-term labor controls at 24-28 gestational weeks.ResultsA total of 333 metabolites were identified and annotated with liquid chromatography/mass spectrometry. Subsequent weighted gene correlation network analysis shows the fatty acid and carene enriched module has a significant positive association (p-value=8e-04) with preterm birth. After controlling for potential clinical confounders, a total of 38 metabolites demonstrated significant changes uniquely associated with preterm birth, where 17 of them were preterm biomarkers. Among seven machine-learning classifiers, application of random forest achieved the highly accurate and specific prediction (AUC = 0.92) for preterm birth in testing data, demonstrating their strong potential as biomarkers for preterm births. The 17 preterm biomarkers are involved in cell signaling, lipid metabolism, and lipid peroxidation functions. Further causality analysis infers that suberic acid upregulates several fatty acids to promote preterm birth.ConclusionsAltogether, this study demonstrates the involvement of lipids, particularly fatty acids, in the pathogenesis of preterm birth.
Covid-19 Vaccination in Pregnancy: A Systematic Review
Authors: Pratama Nando Reza , Wafa Ifan Ali , Budi David Setyo , Putra Manesha , Wardhana Manggala Pasca , Wungu Citrawati Dyah Kencono 
Published: July 2021

AbstractObjectivePregnancy is a risk factor for severe Covid-19. Looking for safe vaccines that evoke protective maternal and fetal antibody response is important.MethodsWe searched from registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the EU Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, and Springer) up until June 20, 2021. Articles were selected based on inclusion and exclusion criteria after duplicates were removed. Infection rate, maternal antibody response, placental antibody transfer, and adverse events were described. This systematic review was performed with quality assessment and semi-quantitative synthesis according to PRISMA guidelines.ResultsTwelve observational studies with a total of 40.509 pregnant women included. The mRNA based vaccines (Pfizer-BioNTech and Moderna) can prevent future SARS-CoV-2 infections (p=0.0004). Both vaccines did not affect pregnancy, delivery, and neonatal outcomes. The most commonly encountered adverse reactions are injection-site pain, fatigue, and headache but only transient. Antibody responses were rapid after the prime dose of vaccines. After booster, antibody responses were higher and associated with better placental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and better antibody transfer ratio.ConclusionsThe Pfizer-BioNTech and Moderna vaccines are efficacious for preventing future SARS-CoV-2 infections. These vaccines can be considered as a safe option for pregnancy and their fetus. Two doses of vaccines were recommended for more robust maternal and fetal antibody responses. Longer latency was associated with higher fetal antibody responses.Systematic Review RegistrationPROSPERO (CRD42021261684)
Dynamics of SARS-CoV-2 host cell interactions inferred from transcriptome analyses
Authors: Adam Lukas , Stanifer Megan , Springer Fabian , Mathony Jan , Di Ponzio Chiara , Eils Roland , Boulant Steeve , Niopek Dominik , Kallenberger Stefan M. 
Published: July 2021

AbstractThe worldwide spread of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) caused an urgent need for an in-depth understanding of interactions between the virus and its host. Here, we dissected the dynamics of virus replication and the host cell transcriptional response to SARS-CoV-2 infection at a systems level by combining time-resolved RNA sequencing with mathematical modeling. We observed an immediate transcriptional activation of inflammatory pathways linked to the anti-viral response followed by increased expression of genes involved in ribosome and mitochondria function, thus hinting at rapid alterations in protein production and cellular energy supply. At later stages, metabolic processes, in particular those depending on cytochrome P450 enzymes, were downregulated. To gain a deeper understanding of the underlying transcriptional dynamics, we developed an ODE model of SARS-CoV-2 infection and replication. Iterative model reduction and refinement revealed that a negative feedback from virus proteins on the expression of anti-viral response genes was essential to explain our experimental dataset. Our study provides insights into SARS-CoV-2 virus-host interaction dynamics and facilitates the identification of druggable host pathways supporting virus replication.
Increased frequency of recurrent in-frame deletions in new expanding lineages of SARS CoV-2 reflects immune selective pressure
Authors: Alisoltani Arghavan , Jaroszewski Lukasz , Iyer Mallika , Iranzadeh Arash , Godzik Adam 
Published: July 2021

AbstractMost of the attention in the surveillance of evolution of SARS-CoV-2 has been centered on single nucleotide substitutions in the spike glycoprotein. We show that in-frame deletions (IFDs) also play a significant role in the evolution of viral genome. The percentage of genomes and lineages with IFDs is growing rapidly and they co-occur independently in multiple lineages, including emerging variants of concerns. IFDs distribution is correlated with spike mutations associated with immune escape and concentrated in proteins involved in interactions with the host immune system. Structural analysis suggests that IFDs remodel viral proteins’ surfaces at common epitopes and interaction interfaces, affecting the virus’ interactions with the immune system. We hypothesize that the increased frequency of IFDs is an adaptive response to elevated global population immunity.SummaryMonitoring of SARS-CoV-2 genome evolution uncovers increased frequency and non-random distribution of in-frame deletions in recently emerged lineages.
Safety and Pharmacokinetics of Intranasally Administered Heparin
Authors: Harris Hannah M. , Boyet Katherine L. , Liu Hao , Dwivedi Rohini , Ashpole Nicole M. , Tandon Ritesh , Bidwell Gene L. , Cheng Zhi , Fassero Lauren A. , Yu Christian S. , Pomin Vitor H. , Mitra Dipanwita , Harrison Kerri A. , Dahl Eric , Gurley Bill J. , Kotha Arun Kumar , Chougule Mahavir Bhupal , Sharp Joshua S. 
Published: July 2021

AbstractPurposeIntranasally administered unfractionated heparin (UFH) and other sulfated polysaccharides are potential prophylactics for COVID-19. The purpose of this research was to measure the safety and pharmacokinetics of clearance of intranasally administered UFH solution from the nasal cavity.MethodsDouble-blinded daily intranasal dosing in C57Bl6 mice with four doses (60 ng to 60 μg) of UFH was carried out for fourteen consecutive days, with both blood coagulation measurements and subject adverse event monitoring. The pharmacokinetics of fluorescent-labeled UFH clearance from the nasal cavity were measured in mice by in vivo imaging. Intranasal UFH at 2000 U/day solution with nasal spray device was tested for safety in a small number of healthy human subjects.ResultsUFH showed no evidence of toxicity in mice at any dose measured. No significant changes were observed in activated partial thromboplastin time (aPTT), platelet count, or frequency of minor irritant events over vehicle-only control. Human subjects showed no significant changes in aPTT time, international normalized ratio (INR), or platelet count over baseline measurements.No serious adverse events were observed. In vivo imaging in a mouse model showed a single phase clearance of UFH from the nasal cavity. After 12 hours, 3.2% of the administered UFH remained in the nasal cavity, decaying to background levels by 48 hours.ConclusionsUFH showed no toxic effects for extended daily intranasal dosing in mice as well as humans. The clearance kinetics of intranasal heparin solution from the nasal cavity indicates potentially protective levels for up to 12 hours after dosing.