bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling the Potential Role of Media Campaigns on the Control of Listeriosis
Authors: Chukwu C. W. , Nyabadza F. , Fatmawati  
Published: December 2020

AbstractHuman Listeria infection is a food-borne disease caused by the consumption of contaminated food products by the bacterial pathogen, Listeria. In this paper, we propose a mathematical model to analyze the impact of media campaigns on the spread and control of Listeriosis. The model exhibited three equilibria namely; disease-free, Listeria-free and endemic equilibria. The food contamination threshold (ℛf) is determined and the local stability analyses of the model discussed. Sensitivity analysis is done to determine the model parameters that most affect the severity of the disease. Numerical simulations were carried out to assess the role of media campaigns on the Listeriosis spread. The results show that; an increase in the intensity of the media awareness campaigns, the removal rate of contaminated food products, a decrease in the contact rate of Listeria by humans results in fewer humans getting infected, thus leading to the disease eradication. An increase in the depletion of media awareness campaigns results in more humans being infected with Listeriosis. These findings may significantly impact policy and decision making in the control of Listeriosis disease.
Relative effectiveness of non-surgical interventions for pain management in knee osteoarthritis: a protocol for a component network meta-analysis of randomised controlled trials
Authors: Thompson Trevor , Ahmed Bawan , Weldon Sharon , Efthimiou Orestis , Stubbs Brendon 
Published: December 2020

ABSTRACTIntroductionKnee osteoarthritis is a chronic degenerative disease and the most common form of osteoarthritis, and is associated with significant chronic pain, disability and impairment of quality of life. Currently, there is no cure for knee osteoarthritis and pain management and improving quality of life are the main therapeutic goals. The objective of this study is to evaluate the relative efficacy and acceptability of currently available interventions using network meta-analysis in order to provide a comprehensive evidence base to guide future clinical treatment guidelines.Methods and analysisA comprehensive literature search of major electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials) and clinical trial registries will be undertaken to identify randomised control trials (RCTs) of interventions listed in NICE guidelines for the treatment of knee osteoarthritis in adults. We will perform a network meta-analysis (NMA) to estimate relative intervention effects across the whole treatment network. If any studies use multicomponent interventions, we will employ a component network meta-analysis (CNMA) model to estimate the contribution of individual components. The quality of evidence will be assessed using the Confidence in Network Meta-Analysis (CINeMA) approach, which is based on the traditional GRADE framework adapted for NMA. Risk of bias will be assessed using the revised Cochrane Risk of Bias (RoB 2.0) tool for RCTs.Ethics and disseminationThis study does not require ethical approval. Findings will be submitted to a peer-reviewed journal.PROSPERO registration numberCRD42020184192.ARTICLE SUMMARYStrengths and limitations of this studyThis will be the first network meta-analysis to assess relative effectiveness of interventions listed in NICE guidelines for pain management in knee osteoarthritisThe study will provide an evidence base to inform future clinical guidelines and treatment decision makingIf relevant data are available, we will estimate the contribution of individual components in multicomponent interventionsQuality of evidence underlying all treatments will be assessedNot all treatments will be evaluated if data are limited or we deem that network meta-analysis assumptions are violated
Psychosocial Factors of Stigma and Relationship to Healthcare Service among Adolescents Living With HIV/AIDS in Kano State, Nigeria
Authors: Amos Oladunni Abimbola , Sina-Odunsi Ayomide Busayo , Nuga Boyiga Bodinga , Adebisi Yusuff Adebayo , Bolarinwa Obasanjo Afolabi , Adeola Adesina Adetoun , Lucero-Prisno Don Eliseo 
Published: December 2020

ABSTRACTBackgroundStigma associated with HIV shapes all aspect of prevention and treatment, yet there are limited data on how HIV-infected adolescents are affected by stigma. Stigma increases risk of psychological problems among HIV-infected individuals which can affect access to treatment and social support services. This study is aimed at identifying psychosocial factors of stigma and relationship to healthcare services among adolescents on antiretroviral therapy (ART) in Gwale Local Government Area (LGA) of Kano state, Nigeria.MethodsA facility based cross-sectional survey was carried out from January 26 to February 28, 2020 across six health facilities providing ART service in Gwale local government. A structured interviewer-administered questionnaire was used to collect the data. ART clients attending clinics were interviewed following an informed verbal consent. Descriptive statistics was used to summarize the data and results are presented using simple frequency tables and percentages. Upon completion of univariate analysis, the data was analyzed at the bivariate level using chi-square test to determine associations between different variables.ResultsOne hundred and eight (108) clients voluntarily participated in the study of which 54 (50%) are male respondents and 54 (50%) are female respondents. Under the internalized stigma item, 67% of HIV-infected adolescents who have lost father or mother to AIDS reported feeling less valuable than other children who are not infected with HIV. Under the perceived stigma items, 86% of participants who have lost father or mother to AIDS reported to have excluded themselves from health services and social activities in the last twelve months due to fear of being insulted. Under the experienced stigma items, 62% of participants who have lost father or mother to AIDS reported to have been avoided by friends and colleagues in the last twelve months.ConclusionThe study revealed that loss of intimate relation (father or mother) to AIDS and equal treatment with other HIV negative siblings were found to be significantly associated with the three forms of stigma (internalized stigma, perceived stigma and experienced stigma) including access to healthcare services. There is need for social and psychological support programs among HIV-infected adolescents.
A Hybrid Catheter Localisation Framework in Echocardiography Based on Electromagnetic Tracking and Deep Learning Segmentation
Authors: Jia Fei , Wang Shu , Pham V. T. 
Published: December 2020

AbstractInterventional cardiology procedure is an important type of minimally invasive surgery that deals with the catheter-based treatment of cardiovascular diseases, such as coronary artery diseases, strokes, peripheral arterial diseases and aortic diseases. Ultrasound imaging, also called echocardiography, is a typical imaging tool that monitors catheter puncturing. Localising a medical device accurately during cardiac interventions can help improve the procedure’s safety and reliability under ultrasound imaging. However, external device tracking and image-based tracking methods can only provide a partial solution. Thus, we proposed a hybrid framework, with the combination of both methods to localise the catheter tip target in an automatic way. The external device used was an electromagnetic tracking system from North Digital Inc (NDI) and the ultrasound image analysis was based on UNet, a deep learning network for semantic segmentation. From the external method, the tip’s location was determined precisely, and the deep learning platform segmented the exact catheter tip automatically.
Bias measurement in, bias results out: how an assumption free height adjusted weight model outperforms body mass index
Authors: Shuey Megan M. , Huang Shi , Levinson Rebecca T. , Farber-Eger Eric , Cahill Katherine N. , Beckman Joshua A. , Koethe John R. , Silver Heidi J. , Niswender Kevin D. , Cox Nancy J. , Harrell Frank E. , Wells Quinn S. 
Published: December 2020

AbstractObjectiveBody mass index (BMI) is the most commonly used predictor of weight-related comorbidities and outcomes. However, the presumed relationship between height and weight intrinsic to BMI may introduce bias with respect to prediction of clinical outcomes. Using Vanderbilt University Medical Center’s deidentified electronic health records and landmark methodology, we performed a series of analyses comparing the performance of models representing weight and height as separate interacting variables to models using BMI.MethodsModel prediction was evaluated with respect to established weight-related cardiometabolic traits, metabolic syndrome and its components hypertension, diabetes mellitus, low high-density lipoprotein, and elevated triglycerides, as well as cardiovascular outcomes, atrial fibrillation, coronary artery disease, heart failure, and peripheral artery disease. Model performance was evaluated using likelihood ratio, R2, and Somers’ Dxy rank correlation. Differences in model predictions were visualized using heatmaps.ResultsRegardless of outcome, the maximally flexible model had a higher likelihood ratio, R2, and Somers’ Dxy rank correlation for event-free prediction probability compared to the BMI model. Performance differed based on the outcome and across the height and weight range.ConclusionsCompared to BMI, modeling height and weight as independent, interacting variables results in less bias and improved predictive accuracy for all tested traits.Study Importance QuestionsWhat is already known about this subject?Body mass index, derived from collected height and weight measures, is an imperfect proxy measure of body fat composition often used in medical research.What are the new findings in your manuscript?We demonstrate how BMI introduces complex non-uniform biases across outcome and height-weight space.How might your results change the direction of research or the focus of clinical practice?Modeling height and weight as separate, non-linear, interacting variables improves clinical prediction across the complete spectrum of heights and weights for all clinical out-comes.
Ferritin nanoparticle based SARS-CoV-2 RBD vaccine induces persistent antibody response and long-term memory in mice
Authors: Wang Wenjun , Huang Baoying , Zhu Yanping , Tan Wenjie , Zhu Mingzhao 
Published: December 2020

ABSTRACTSince the outbreak of COVID-19, over 200 vaccine candidates have been documented and some of them have advanced to clinical trials with encouraging results. However, the antibody persistence over 3 months post immunization and the long-term memory have been rarely reported. Here, we report that a ferritin nanoparticle based SARS-CoV-2 RBD vaccine induced in mice an efficient antibody response which lasts for at least 7 months post immunization. Significantly higher number of memory B cells were maintained and a significantly higher level of recall response was induced upon antigen challenge. Thus, we believe our current study provide the first information about the long-term antibody persistence and memory response of a COVID-19 vaccine. This information would be also timely useful for the development and evaluation of other vaccines.
Cell-intrinsic effects of TorsinA(ΔE) disrupt dopamine release in a mouse model ofDYT1-TOR1Adystonia
Authors: Downs Anthony M. , Fan Xueliang , Kadakia Radhika , Donsante Yuping , Jinnah H.A. , Hess Ellen J. 
Published: December 2020

ABSTRACTDYT1-TOR1Adystonia is an inherited dystonia caused by a three base-pair deletion in theTOR1Agene (TOR1AΔE). Although the mechanisms underlying the dystonic movements are largely unknown, abnormalities in striatal dopamine and acetylcholine neurotransmission are consistently implicated whereby dopamine release is reduced while cholinergic tone is increased. Because striatal cholinergic neurotransmission mediates dopamine release, it is not known if the dopamine release deficit is mediated indirectly by abnormal acetylcholine neurotransmission or ifTor1a(ΔE)acts directly within dopaminergic neurons to attenuate release. To dissect the microcircuit that governs the deficit in dopamine release, we conditionally expressedTor1a(ΔE)in either dopamine neurons or cholinergic interneurons in mice and assessed striatal dopamine release usingex vivofast scan cyclic voltammetry or dopamine efflux usingin vivomicrodialysis. Conditional expression ofTor1a(ΔE)in cholinergic neurons did not affect striatal dopamine release. In contrast, conditional expression ofTor1a(ΔE)in dopamine neurons reduced dopamine release to 50% of normal, which is comparable to the deficit inTor1a+/ΔEknockin mice that express the mutation ubiquitously. Despite the deficit in dopamine release, we found that theTor1a(ΔE)mutation does not cause obvious nerve terminal dysfunction as other presynaptic mechanisms, including electrical excitability, vesicle recycling/refilling, Ca2+signaling, D2 dopamine autoreceptor function and GABABreceptor function, are intact. Although the mechanistic link betweenTor1a(ΔE)and dopamine release is unclear, these results clearly demonstrate that the defect in dopamine release is caused by the action of theTor1a(ΔE)mutation within dopamine neurons.
A role for cerebral cortex in the suppression of innate defensive behavior
Authors: Natale Silvia , Masferrer Maria Esteban , Deivasigamani Senthilkumar , Gross Cornelius T. 
Published: December 2020

AbstractThe cerebral cortex is involved in the control of cognition and the processing of learned information and it appears to have a role in the adaptation of behavior in response to unpredictable circumstances. In addition, the cortex may have a role in the regulation of innate responses since rodents, cats or primates with surgical removal or accidental destruction of cortical regions show excessive irritability, aggression and rage elicited by threatening stimuli. However, it remains unclear whether cortex has an acute role in suppressing innate threat responses because the imprecision and chronic nature of these lesions leaves open the possibility that compensatory processes may underlie some of these phenotypes. In the present study we used pharmacogenetic inhibition to precisely, rapidly and reversibly suppress cortical pyramidal neuron function and examine its contribution to defensive behaviors elicited by a variety of innately aversive stimuli. Inhibition of cortex caused an increase of defensive responses elicited by an aggressive conspecific, a novel prey, and a physically stressful stimulus. These findings are consistent with a role of cortex in the acute inhibition of innate defensive behaviors.
InVivoPharmacokinetic Study of Remdesivir Dry Powder for Inhalation in Hamsters
Authors: Sahakijpijarn Sawittree , Moon Chaeho , Warnken Zachary N. , Maier Esther Y. , DeVore Jennie E. , Christensen Dale J. , Koleng John J. , Williams Robert O. 
Published: December 2020

AbstractRemdesivir dry powder for inhalation was previously developed using thin film freezing (TFF). A single-dose 24-hour pharmacokinetic study in hamsters, a small animal model for SARS-CoV-2, demonstrated that pulmonary delivery of TFF remdesivir can achieve plasma remdesivir and GS-441524 levels higher than the reported EC50s of both remdesivir and GS-441524 (in human epithelial cells) over 20 hours. The half-life of GS-4412524 following dry powder insufflation was about 7 hours, suggesting the dosing regimen would be twice daily administration. Although the remdesivir-Captisol®(80/20 w/w) formulation showed faster and greater absorption of remdesivir and GS-4412524 in the lung, remdesivir-leucine (80/20 w/w) exhibited a greater Cmaxwith shorter Tmaxand lower AUC of GS-441524, indicating lower total drug exposure is required to achieve a high effective concentration against SAR-CoV-2. In conclusion, remdesivir dry powder for inhalation would be a promising alternative dosage form for the treatment of COVID-19 disease.
Multi-scale annotations of chromatin states in 127 human cell-types
Authors: Kai Yan , Tsoucas Stephanos , Suo Shengbao , Yuan Guo-Cheng 
Published: December 2020

AbstractGenome-wide profiling of chromatin states has been widely used to characterize the biological function of non-coding genomic sequences in a cell-type specific manner. However, the systematic, comprehensive annotations of chromatin states from experimental data are challenging and require not just extensive biological knowledge but also sophisticated computational modeling. Previously we developed a hierarchical hidden Markov model, named diHMM, to systematically annotate chromatin states at multiple scales based on the combination of histone mark and chromatin regulator binding profiles. Here, we have improved the method by optimizing computational efficiency and using an ensemble-clustering approach to achieve a unified annotation by integrating information from cell-type-specific models. We then applied this improved method to generate a unified multi-scale chromatin state map in 127 human cell types, based on public data generated by the Epigenome Roadmap and ENCODE consortia. We found cell types with similar origin are typically associated with similar chromatin states, but cultured cell lines have distinct structures than primary cells. The contribution of enhancer elements to gene regulation is mediated by the broader context of domain-state organization. Distinct domain-state patterns are associated with various 3D chromatin structures. As such, we have demonstrated the utility of the multi-scale chromatin state map in characterizing the biological function of the human genome.
Hydrating the Respiratory Tract: An Alternative Explanation Why Masks Lower Severity of COVID-19 Disease
Authors: Courtney Joseph M. , Bax Ad 
Published: December 2020

AbstractSeasonality of respiratory diseases has been linked, among other factors, to low outdoor absolute humidity and low relative humidity in indoor environments, which increase evaporation of water in the mucosal layer lining the respiratory tract. We demonstrate that normal breathing results in an absorption-desorption cycle inside facemasks, where super-saturated air is absorbed by the mask fibers during expiration, followed by evaporation during inspiration of dry environmental air. For double-layered cotton masks, which have considerable heat capacity, the temperature of inspired air rises above room temperature, and the effective increase in relative humidity can exceed 100%. We propose that the recently reported, disease-attenuating effect of generic facemasks is dominated by the strong humidity increase of inspired air.SIGNIFICANCE STATEMENTFacemasks are the most widely used tool for mitigating the spread of the COVID-19 pandemic. Decreased disease severity by the wearer has also been linked to the use of cloth facemasks. This well-documented finding is surprising considering that such masks are poor at filtering the smallest aerosol particles, which can reach the lower respiratory tract and have been associated with severe disease. We show that facemasks strongly increase the effective humidity of inhaled air, thereby promoting hydration of the respiratory epithelium which is known to be beneficial to the immune system. Increased humidity of inspired air could be an alternate explanation for the now well-established link between mask wearing and lower disease severity.
Assessing the usage of indirect motor pathways following a hemiparetic stroke
Authors: Tian Runfeng , Dewald Julius P.A. , Yang Yuan 
Published: December 2020

AbstractA hallmark impairment in a hemiparetic stroke is a loss of independent joint control resulting in abnormal co-activation of shoulder abductor and elbow flexor muscles in their paretic arm, clinically known as the flexion synergy. The flexion synergy appears while generating shoulder abduction (SABD) torques as lifting the paretic arm. This likely be caused by an increased reliance on contralesional indirect motor pathways following damage to direct corticospinal projections. The assessment of functional connectivity between brain and muscle signals, i.e., brain-muscle connectivity (BMC), may provide insight into such changes to the usage of motor pathways. Our previous model simulation shows that multi-synaptic connections along the indirect motor pathway can generate nonlinear connectivity. We hypothesize that increased usage of indirect motor pathways (as increasing SABD load) will lead to an increase of nonlinear BMC. To test this hypothesis, we measured brain activity, muscle activity from shoulder abductors when stroke participants generate 20% and 40% of maximum SABD torque with their paretic arm. We computed both linear and nonlinear BMC between EEG and EMG. We found dominant nonlinear BMC at contralesional/ipsilateral hemisphere for stroke, whose magnitude increased with the SABD load. These results supported our hypothesis and indicated that nonlinear BMC could provide a quantitative indicator for determining the usage of indirect motor pathways following a hemiparetic stroke.
Engineered CRISPR/Cas12a Enables Rapid SARS-CoV-2 Detection
Authors: Nguyen Long T. , Rananaware Santosh R. , Pizzano Brianna L.M. , Stone Brandon T. , Jain Piyush K. 
Published: December 2020

ABSTRACTThe coronavirus disease (COVID-19) caused by SARS-CoV-2 has swept through the globe at an unprecedented rate. CRISPR-based detection technologies such as DETECTR, SHERLOCK, and STOPCovid have emerged as a rapid and affordable platform that can shape the future of diagnostics. Recently, we reported engineered crRNAs for Cas12a, called ENHANCE, that enables enhanced detection of nucleic acids. Here we report development, clinical validation, and advancement of ENHANCE platform for detecting SARS-CoV-2. With an RT-LAMP pre-amplification step, ENHANCE detects samples down to a single copy with 95% accuracy and shows high specificity towards various isolates of SARS-CoV-2 against 31 highly similar and common respiratory pathogens. Utilizing LbCas12a-mediated trans-cleavage activity, ENHANCE works robustly in a wide range of magnesium concentration (3 mM-13 mM), allowing for further assay optimization. Additionally, ENHANCEv2 is developed to further improve the previously reported ENHANCE. ENHANCEv2 employs mutated LbCas12aD156R, engineered chimeric DNA-extended crRNA, and a dual reporter for both fluorescence-based reporter assay and lateral flow assay. Both ENHANCE and ENHANCEv2 are validated in 62 clinical nasopharyngeal swabs, showing 60/62 (96.7%) agreement with RT-qPCR results, and using only 5 μL of sample and 20 minutes of CRISPR reaction. Lateral flow assay on paper strips displays 100% agreement with fluorescence-based reporter assay in the clinical validation. Following a 30-minute pre-amplification RT-LAMP step, the lyophilized ENHANCEv2 is shown to achieve high sensitivity and specificity while reducing CRISPR reaction time to as low as 3 minutes and maintaining its detection capability upon storage at room temperature for several weeks.